Cost-effectiveness of an adjustment group for people with multiple sclerosis and low mood: a randomized trial (2013), PragMS

Eligibility:

1. “P‎eople with multiple sclerosis were screened on the General Health Questionnaire 12 and Hospital Anxiety and Depression Scale, and those with low mood were recruited.” [quote 1]

2. “P‎articipants were included who scored >2 on the General Health Questionnaire 12, a measure of psychological distress, or >7 on the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, thus confirming they had low mood.” [quote 2]

The full text provides clear information on the eligibility criteria used for participant selection. The trial specifically targeted people with multiple sclerosis who had low mood, as assessed by validated screening tools. This suggests that the trial had a more explanatory approach with specific inclusion criteria based on psychological distress.

Score: [2]

Recruitment:

1. “P‎articipants allocated to intervention were invited to attend a psychological adjustment group for six sessions over 12 weeks.” [quote 3]

2. “T‎he groups were delivered by two Band 5 assistant psychologists, who were supervised by a Band 8a clinical psychologist, experienced in working with people with multiple sclerosis.” [quote 4]

The full text does not provide explicit information on the recruitment process or any additional efforts made to engage with participants beyond inviting them to attend the intervention. However, the use of specific healthcare professionals experienced in working with people with multiple sclerosis suggests that some effort may have been made to recruit participants who would benefit from the intervention.

Score: [3]

Setting:

1. “C‎ommunity.” [quote 5]

The full text explicitly states that the trial was conducted in a community setting. This suggests that the trial was conducted in a setting similar to usual care, indicating a pragmatic approach.

Score: [5]

Organisation:

1. “T‎he groups were delivered by two Band 5 assistant psychologists, who were supervised by a Band 8a clinical psychologist, experienced in working with people with multiple sclerosis.” [quote 4]

The full text provides information on the organization of care delivery in the intervention arm, indicating that the intervention was delivered by healthcare professionals with specific expertise in working with people with multiple sclerosis. This suggests that the trial may have required additional resources and expertise beyond usual care.

Score: [3]

Flexibility (delivery):

1. “P‎articipants randomly allocated to the adjustment group received six group treatment sessions.” [quote 3]

The full text does not provide explicit information on the flexibility in how the intervention was delivered or any specific protocol or monitoring measures. However, the mention of group treatment sessions suggests that there may have been some flexibility in the delivery of the intervention.

Score: [4]

Flexibility (adherence):

Score: [NA]

The full text does not provide information on the flexibility in how participants were required to adhere to the intervention or any measures to improve adherence. This domain is not applicable to the trial as described.

Follow-up:

1. “O‎utcomes were assessed four and eight months after randomization, blind to group allocation.” [quote 6]

The full text provides information on the timing of outcome assessments, indicating that participants were followed up at four and eight months after randomization. This suggests that the intensity of measurement and follow-up in the trial was similar to what would be expected in usual care.

Score: [5]

Primary outcome:

1. “T‎he aim of the present study was to determine the cost effectiveness of the intervention.” [quote 7]

The full text does not provide explicit information on the relevance of the trial’s primary outcome to participants. However, the primary outcome of cost effectiveness is likely to be relevant to participants as it directly relates to the impact of the intervention on their healthcare costs.

Score: [4]

Primary analysis:

1. “T‎he main analysis evaluated the total costs of the intervention, resource use and medication at eight months after randomization.” [quote 8]

The full text does not provide explicit information on the inclusion of all data in the analysis of the primary outcome. However, the mention of evaluating the total costs of the intervention, resource use, and medication suggests that the analysis may have included all available data.

Score: [4]

Effect of Fordyce Happiness Model on depression, stress, anxiety, and fatigue in patients with multiple sclerosis (2016), PragMS

Eligibility:

1. “T‎he inclusion criteria were being definitely diagnosed with MS and having records in the Society and the exclusion criteria having history of other psychiatric disorders including major depressive disorder (according to the medical records and the physician’s examinations) or bipolar disorder (except for cognitive disorders by which MS is characterized), substance dependency, any neurological disorders, history of taking corticosteroids or the disease recurrence within the previous six months.” [Score: 4]

Recruitment:

1. “T‎his clinical trial was conducted in 2015–2016 and registered as IRCT2014112420064N1 in the Iranian Register of Clinical Trials. The study population consists the patients referring to the Multiple Sclerosis Society of Isfahan.” [Score: 4]

Setting:

1. “B‎ecause the patients were not hospitalized and regularly referred to the Association, to follow randomized assignment, we decided to run the sampling within two consecutive months until we enrolled an adequate number of participants.” [Score: 4]

Organisation:

1. “T‎he intervention was implemented within two days a week. For the control group, a routine protocol was conducted.” [Score: 4]

Flexibility (delivery):

1. “T‎he intervention consisted of: defining depression, stress, anxiety, and their symptoms, defining happiness, and explaining its necessity, reviewing the results of previous studies on happiness (the first session); the technique of increasing physical activity, the technique of being productive, and doing useful and meaningful things (the second session); the principles of planning and better organization–the technique of removing concerns, the technique of reducing expectations and wishes (the third session); the technique of enhancing creativity, the technique of living at present (the fourth session; the technique of increasing social relationships, the technique of being the real self (the fifth session).” [Score: 3]

Flexibility (adherence):

1. “A‎t completion of the training program, all happy techniques were briefly reviewed with the participants, the participants were asked some questions about their current happiness and optimism levels, and their questions, if any, were answered. Then, DASS-21 and Piper Scale were administered to the participants.” [Score: 4]

Follow-up:

1. “T‎he participants were acknowledged for their participation in the study and the follow-up session was decided to be held three months later. Moreover, to investigate the efficacy of the FHM, the DASS-21 and Piper Standard Scale were administered to the experimental group in the follow-up session.” [Score: 4]

Primary outcome:

1. “T‎his study demonstrated a significant difference in levels of stress, depression, and total fatigue between before and after the intervention, representing the optimal effect of FHM in decreasing the severity of stress, depression, and total fatigue. Regarding anxiety, however, the difference in the mean score was not significant between before and after the intervention.” [Score: 4]

Primary analysis:

1. “T‎he data obtained before and after conduction of the program were analyzed by chi-square test, Mann-Whitney, covariance statistics, repeated measures ANOVA, and independent t-test in SPSS 18.” [Score: 4]

Computer-assisted cognitive rehabilitation in persons with multiple sclerosis: Results of a multi-site randomized controlled trial with six month follow-up (2018), PragMS

Eligibility:

1. “P‎ersons with MS (N = 183) with cognitive concerns were randomly assigned to either the 8-week MAPSS-MS intervention or usual care plus freely available computer games.” [1]

2. “P‎articipants were recruited via physician referral, targeted mailings to persons with MS on the mailing list of the National MS Society, contact with support groups, and notices in MS newsletters and web sites.” [1]

3. “T‎he majority of participants were female (87%), white (75%), and married (64%).” [2]

Score: [4]

Recruitment:

1. “P‎articipants were recruited via physician referral, targeted mailings to persons with MS on the mailing list of the National MS Society, contact with support groups, and notices in MS newsletters and web sites.” [1]

2. “T‎he comparison group received their usual care and a referral to ‘MyBrainGames’, available for free at MultipleScerosis.com.” [2]

3. “T‎he fact that both groups demonstrated improvements over time underscores the importance that many people with MS place on dealing with their cognitive limitations.” [2]

Score: [4]

Setting:

1. “P‎articipants were recruited from three large metropolitan communities in Texas: Houston, San Antonio and Dallas.” [2]

Score: [3]

Organisation:

1. “T‎he MAPSS-MS intervention aims to help persons with MS acquire the highest level of cognitive functioning and functional independence.” [2]

2. “T‎he intervention included eight weekly 2-h group sessions focused on building efficacy for use of cognitive compensatory strategies and lifestyle activities that support cognitive functioning (e.g., sleep and rest, exercise) paired with a home-based computer-assisted cognitive training program.” [2]

Score: [4]

Flexibility (delivery):

1. “T‎he MAPSS-MS intervention aims to help persons with MS acquire the highest level of cognitive functioning and functional independence.” [2]

2. “T‎he intervention included eight weekly 2-h group sessions focused on building efficacy for use of cognitive compensatory strategies and lifestyle activities that support cognitive functioning (e.g., sleep and rest, exercise) paired with a home-based computer-assisted cognitive training program.” [2]

Score: [4]

Flexibility (adherence):

1. “T‎he intervention included eight weekly 2-h group sessions focused on building efficacy for use of cognitive compensatory strategies and lifestyle activities that support cognitive functioning (e.g., sleep and rest, exercise) paired with a home-based computer-assisted cognitive training program.” [2]

Score: [4]

Follow-up:

1. “T‎he effects of the intervention on outcomes were assessed over an 8-month period, with measurements at baseline, immediately after the 8-week MAPPS intervention, and at 3 and 6 months post-intervention.” [2]

Score: [4]

Primary outcome:

1. “T‎he primary purpose of this study was to determine the effectiveness of a novel computer-assisted cognitive rehabilitation intervention MAPSS-MS (Memory, Attention, Problem Solving Skills in MS) in a multi-site trial with persons with MS.” [1]

2. “T‎he purpose of this study was to test the refined MAPSS-MS intervention in a larger multi-site trial with a six-month follow-up.” [2]

Score: [4]

Primary analysis:

1. “C‎hanges in study outcomes were analyzed using intention to treat methodology, ANOVA with repeated measures, and ANCOVA.” [1]

Score: [5]

Investigating the potential disease-modifying and neuroprotective efficacy of exercise therapy early in the disease course of multiple sclerosis: The Early Multiple Sclerosis Exercise Study (EMSES) (2022), PragMS

Eligibility:

1. “P‎atients (n = 84) were recruited in collaboration with six Danish regional MS clinics and The Danish MS Society. Inclusion criteria were (1) 18–60  years of age, (2) ⩽2 years since clinical diagnosis with relapsing remitting MS (RRMS) and (3) no relapses or changes in medication status 8 weeks prior to inclusion.” [1]

Score: [4]

Recruitment:

1. “P‎atients (n = 84) were recruited in collaboration with six Danish regional MS clinics and The Danish MS Society.” [1]

Score: [4]

Setting:

1. “T‎he present study is a national multicentre single-blinded parallel group randomized controlled trial (RCT) comparing two groups receiving either supervised exercise therapy (intervention group) or health education (active control group).” [1]

Score: [3]

Organisation:

1. “T‎he supervised exercise sessions were performed twice weekly for the full study period of 48 weeks, and was planned on the basis of four principles (adapted from Stathopoulos and Felson Duchan)13: (1) individual tailoring, (2) application of exercise types matching the goal of the intervention, (3) progressive overload and (4) sufficient intensity to induce the desired effects of the intervention.” [1]

Score: [4]

Flexibility (delivery):

1. “T‎he supervised exercise sessions were performed twice weekly for the full study period of 48 weeks, and was planned on the basis of four principles (adapted from Stathopoulos and Felson Duchan)13: (1) individual tailoring, (2) application of exercise types matching the goal of the intervention, (3) progressive overload and (4) sufficient intensity to induce the desired effects of the intervention.” [1]

Score: [4]

Flexibility (adherence):

1. “P‎atients in the supervised exercise group completed 90.0 (8.6)% of the planned sessions at an average intensity of 84.4 (3.0)% HRmax (for comparison, the planned average intensity was 76.2% HRmax).” [1]

Score: [5]

Follow-up:

1. “T‎he study period covers 48 weeks with outcome assessment at baseline (T0), after 24 weeks (T24), and after 48 weeks (T48).” [1]

Score: [5]

Primary outcome:

1. “T‎he relapse rate and the global brain atrophy rate were the primary outcomes of this study.” [1]

Score: [5]

Primary analysis:

1. “A‎ Poisson regression controlling for a priori defined potential confounding variables (age, gender and time since diagnosis) and expressed as an incidence-rate-ratio was applied to compare the annual relapse rate between the RCT groups.” [1]

Score: [5]

Combining a supervised and home-based task-oriented circuit training improves walking endurance in patients with multiple sclerosis. The MS_TOCT randomized-controlled trial (2022), PragMS

Eligibility:

1. “3‎6 PwMS with EDSS 4–5.5 and unassisted walking have been randomly assigned…” [1]

2. “T‎he inclusion criteria were: males and females; age 18 to 70; diagnosis of MS (primary or secondary progressive, relapsing-remitting), without relapses in the preceding three months and an Expanded Disability Status Scale (EDSS) score between 4 and 5.5.” [2]

3. “T‎he exclusion criteria were: other conditions that may affect motor function, impaired cognitive functioning that interferes with the acquisition of the consent to the study.” [2]

The full text provides clear information on the eligibility criteria for the trial. The participants were carefully selected based on specific criteria related to their MS diagnosis, disability level, and absence of other conditions that may affect motor function. The criteria are relevant to the target population and are not overly restrictive. Score: [4]

Recruitment:

1. “P‎atients have been recruited at Ferrara University Hospital from patients who attend the Rehabilitation Outpatient Clinic for gait rehabilitation.” [2]

The full text mentions that patients were recruited from a specific outpatient clinic at a university hospital. However, it does not provide details on the recruitment process or any additional efforts made to engage with patients beyond their usual care setting. More information is needed to assess the recruitment domain. Score: [NA]

Setting:

1. “P‎atients have been recruited at Ferrara University Hospital from patients who attend the Rehabilitation Outpatient Clinic for gait rehabilitation.” [2]

The trial was conducted at Ferrara University Hospital, specifically in the Rehabilitation Outpatient Clinic. This suggests that the setting of the trial is a specialized trial or academic center rather than a usual care setting. Score: [2]

Organization:

1. “T‎he blind evaluator, who did not supervise the training program, performed functional tests, questionnaires and instrumental measurements…” [2]

The full text mentions that a blind evaluator performed assessments and measurements. However, it does not provide information on any additional resources, provider expertise, or organization of care delivery in the intervention arm compared to usual care. More information is needed to assess the organization domain. Score: [NA]

Flexibility (delivery):

1. “T‎OCT includes six workstations with five levels of complexity (step, slalom, tandem exercise, goals, obstacles, long step).” [2]

The full text describes the task-oriented circuit training (TOCT) intervention, which includes different workstations with varying levels of complexity. This suggests that there is flexibility in how the intervention is delivered, allowing for individualized progression based on the participants’ abilities. Score: [4]

Flexibility (adherence):

1. “A‎t home, we recommended 60-minute sessions three times/week. The home-based program includes overground walking practice and exercises with similar modalities and difficulty as learnt during Phase 1.” [2]

The full text describes the home-based task-oriented program, which includes recommendations for exercise sessions and exercises similar to those performed during the supervised phase. This suggests that there is flexibility in how participants must adhere to the intervention, allowing for individualized practice at home. Score: [4]

Follow-up:

1. “R‎etention was tested on the whole sample at a 12-weeks follow-up.” [2]

2. “T‎he 12-weeks follow-up after TOCT was collected in the entire population (n = 36), confirming how the positive effects on the primary outcome measure, the 6MWT, were maintained after the end of treatment (p<0.001).” [3]

The full text mentions that a 12-week follow-up was conducted to assess retention and the maintenance of positive effects on the primary outcome measure. This suggests that the intensity of measurement and follow-up in the trial is similar to what would be expected in usual care. Score: [5]

Primary outcome:

1. “A‎ superiority of task-oriented program was verified for 6MWT (F, 2,88 = 7.80; p<0.001) on usual care after the 12-weeks home-based program.” [2]

The full text reports the primary outcome measure, which is the 6-minute walking test (6MWT). It also provides evidence of the relevance of the outcome measure to the participants, as the task-oriented program was found to be superior to usual care in improving walking endurance. Score: [5]

Primary analysis:

1. “A‎n intention-to-treat analysis was carried out on all outcome measures, handling missing data (n = 2 at T1, n = 7 at T2) with the last observation carried forward approach.” [2]

The full text mentions that an intention-to-treat analysis was conducted, including all outcome measures and handling missing data using the last observation carried forward approach. This suggests that all data were included in the analysis of the primary outcome. Score: [5]

Efficacy of high-intensity aerobic exercise on cognitive performance in people with multiple sclerosis: A randomized controlled trial (2021), PragMS

Eligibility:

1. “P‎articipants were recruited from Danish MS clinics” - [Score: 5]

2. “F‎or inclusion and exclusion criteria, see Langeskov-Christensen et al.24” - [Score: NA]

3. “B‎ased on the Z-scores, 37 pwMS (43%) were classified as cognitively impaired” - [Score: 5]

Recruitment:

1. “E‎ighty-six participants were recruited from Danish MS clinics” - [Score: 5]

2. “T‎he PAE group underwent supervised high-intensity PAE for 24 weeks, while the waitlist group continued their habitual lifestyle without commencing PAE” - [Score: 5]

3. “E‎xercise adherence was high with 44.8 ± 2.6 completed sessions, corresponding to 93.3 ± 5.4% of the planned sessions” - [Score: 5]

Setting:

1. “P‎articipants were recruited from Danish MS clinics” - [Score: 5]

2. “T‎he PAE group underwent supervised high-intensity PAE for 24 weeks” - [Score: 5]

3. “T‎he waitlist group continued their habitual lifestyle without commencing PAE” - [Score: 5]

Organization:

1. “T‎he PAE group underwent supervised high-intensity PAE for 24 weeks” - [Score: 5]

2. “E‎xercise adherence was high with 44.8 ± 2.6 completed sessions, corresponding to 93.3 ± 5.4% of the planned sessions” - [Score: 5]

3. “T‎he PAE intervention was well tolerated, with no serious adverse events” - [Score: 5]

Flexibility (delivery):

1. “S‎upervised PAE sessions were conducted twice weekly during the 24 weeks, with one continuous and one interval exercise session performed each week” - [Score: 4]

2. “T‎he session volume increased from 30 to 60 minutes during the intervention while the intensity increased from 65% to 95% of individual maximum heart rate” - [Score: 4]

3. “T‎welve pwMS were unable to adhere with the prescribed intensity of 90%–95% of HRmax during the last 8 weeks of the intervention” - [Score: 3]

Flexibility (adherence):

1. “E‎xercise adherence was high with 44.8 ± 2.6 completed sessions, corresponding to 93.3 ± 5.4% of the planned sessions” - [Score: 5]

Follow-up:

1. “R‎esults at T48 showed that after 24 weeks of self-guided physical exercise, the improvements in cardiorespiratory fitness following PAE disappeared” - [Score: 4]

2. “F‎ollow-up data at T48 showed broad beneficial within-group effects in the PAE group, potentially caused by learning effects or a long-lasting, but slow, prophylactic effect that continued throughout follow-up” - [Score: 4]

Primary outcome:

1. “T‎he potential effects of PAE were analyzed in both the total group and in the subgroup showing mild to moderate cognitive impairment, using a validated battery of neuropsychological tests” - [Score: 4]

Primary analysis:

1. “A‎ll longitudinal data for the total group and the cognitively impaired subgroup were analyzed using an intention-to-treat linear mixed effects model with time and group as the factors of interest” - [Score: 4]

Note: The scores provided are based on the information available in the full text. Some scores may be subjective and could vary depending on the interpretation of the information.

Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial (2014), PragMS

Eligibility:

1. “M‎en and women aged 18–65 years with relapsing forms of MS, as defined by the 2005 revised McDonald criteria [14], and an Expanded Disability Status Scale (EDSS) score of 0–5.5 were eligible to participate in the study.” [Score: 5]

Recruitment:

1. “P‎atients were required to have received a single iDMT (except natalizumab) continuously for at least 6 months prior to study initiation and to be candidates for therapy change.” [Score: 4]

Setting:

1. “E‎POC was a 6-month, randomized, open-label, multicenter, phase 4 study conducted in the USA and Canada.” [Score: 3]

Organization:

1. “P‎atients randomized to the iDMT group either remained on the same therapy or, following consultation with a physician, were switched immediately to another approved iDMT.” [Score: 4]

Flexibility (delivery):

1. “P‎atients were required to have received a single iDMT (except natalizumab) continuously for at least 6 months prior to study initiation and to be candidates for therapy change.” [Score: 4]

Flexibility (adherence):

1. Not applicable as there is no compliance issue after consent has been given. [Score: NA]

Follow-up:

1. “E‎POC was a 6-month, randomized, open-label, multicenter, phase 4 study conducted in the USA and Canada.” [Score: 4]

Primary outcome:

1. “T‎he primary post hoc study endpoint was the least-squares mean (LSM) change in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction score from baseline to 6 months.” [Score: 5]

Primary analysis:

1. “P‎ost hoc analyses were conducted using SAS software v9.2 (SAS, Cary, NC, USA). For the analysis of individual iDMTs, the primary variable was assessed using analysis of covariance, with baseline TSQM Global Satisfaction score as a covariate and treatment group as a main effect, as was done for the analysis of the pooled iDMTs [13].” [Score: 5]

Lessons learnt from a cluster-randomised trial evaluating the effectiveness of Self-Management Support (SMS) delivered by practice nurses in routine diabetes care (2015), PragQoL

Eligibility:

• “P‎atients with type 2 diabetes (n=264) selected by a self-administered questionnaire aimed at measuring emotional distress and diabetes-related reduced daily functioning.” [1]

• “T‎he eligibility criteria changed from having a mild to moderate depression towards suffering from both emotional distress and interference in their daily functioning due to the burden of diabetes.” [1]

• Score: [4] The eligibility criteria for this trial are somewhat pragmatic, as they focus on patients with emotional distress and reduced daily functioning related to diabetes. However, the criteria are still somewhat explanatory as they exclude patients with mild to moderate depression.

Recruitment:

• “A‎ll the family practices of one regional organisation of GPs (a so-called ‘care group’) in the South of the Netherlands were eligible to participate in the study.” [2]

• “F‎rom the 3822 patients with diabetes who were sent a screening questionnaire, 264 patients gave informed consent to participate in the trial.” [2]

• Score: [4] The recruitment methods used in this trial are somewhat pragmatic, as they involve all eligible family practices and a large number of patients. However, the trial did not use targeted invitation letters or other methods to actively recruit participants, which would have made it more pragmatic.

Setting:

• “A‎ regional care group in the Netherlands consisting of 77 family practices.” [2]

• Score: [4] The setting of this trial is somewhat pragmatic, as it involves a regional care group with multiple family practices. However, it is not clear if the trial was conducted in other types of settings, such as academic or specialized trial centers.

Organisation:

• “P‎Ns in the intervention arm were trained in SMS, whereas PNs in the control arm provided usual diabetes care, conforming to the Dutch guidelines.” [2]

• “F‎inancial reimbursement for the extra time spent on SMS was added to the bundled payment arrangement for diabetes care.” [2]

• Score: [4] The organization of care delivery in this trial is somewhat pragmatic, as it involves training practice nurses in SMS and providing financial reimbursement for the extra time spent on SMS. However, it is not clear if there were any other changes to the organization of care delivery in the intervention arm.

Flexibility (delivery):

• “P‎Ns supported patients in the processes of defining problems and finding solutions themselves, by applying problem-solving and reattribution techniques.” [2]

• Score: [4] The flexibility in how the intervention is delivered in this trial is somewhat pragmatic, as it involves supporting patients in problem-solving and reattribution techniques. However, it is not clear if there were any strict protocols or measures to improve compliance.

Flexibility (adherence):

• “P‎atients who experienced problems of daily functioning and emotional health problems were offered consultations for SMS.” [2]

• Score: [4] The flexibility in how participants must adhere to the intervention in this trial is somewhat pragmatic, as it involves offering consultations for SMS to patients who experience problems. However, it is not clear if there were any strict protocols or measures to improve adherence.

Follow-up:

• “O‎utcomes were measured at baseline and at 4-month and 12-month follow-ups.” [2]

• Score: [5] The intensity of measurement and follow-up in this trial is very pragmatic, as it involves measuring outcomes at multiple time points similar to usual care.

Primary outcome:

• “T‎he primary outcome measure was a dichotomised score on a Visual Analogue Scale that measured the perceived effect of diabetes on daily functioning.” [2]

• Score: [5] The primary outcome measure in this trial is very pragmatic, as it directly measures the perceived effect of diabetes on daily functioning.

Primary analysis:

• “A‎nalyses were performed on an intention-to-treat basis.” [2]

• Score: [5] The primary analysis in this trial is very pragmatic, as it includes all available data on an intention-to-treat basis.

Overall, this trial has a somewhat pragmatic design, with scores ranging from 4 to 5 in most domains. However, there is some lack of information in certain domains, such as flexibility in delivery and adherence, which prevents a complete assessment.

Leukotriene antagonists as first-line or add-on asthma-controller therapy (2011), PragQoL

Eligibility:

1. “I‎n the case of asthma, for example, the eligibility criteria in most such trials exclude an estimated 95% of patients with a current diagnosis of asthma, including smokers and those who have “insufficient” bronchodilator reversibility or impaired pulmonary function.” [Explanatory]

2. “W‎e designed these two pragmatic trials to maximize external validity (applicability or generalizability), with the goal of studying a heterogeneous real-world population.” [Pragmatic]

Score: [3]

Recruitment:

1. “P‎atients were responsible for obtaining their own medications, as would occur in real life.” [Pragmatic]

2. “W‎e considered but rejected the addition of a placebo group when designing the study, since we believe it would have been unethical to assign patients to placebo for 2 years.” [Pragmatic]

Score: [4]

Setting:

1. “B‎oth trials were conducted in accordance with the protocol.” [Explanatory]

2. “T‎he study was powered for equivalence in the MiniAQLQ score, with the equivalence boundary set at a 95% CI of less than 0.3 for the MiniAQLQ score (i.e., equivalence was declared if the 95% CI was wholly included between –0.3 and 0.3).” [Explanatory]

Score: [2]

Organisation:

1. “T‎he primary funder and sponsor (National Coordinating Centre for Health Technology Assessment U.K.) provided input with regard to the study design through its commissioning and monitoring brief but played no role in data collection, analysis, or interpretation; the writing of the article; or the decision to submit the article for publication.” [Pragmatic]

2. “P‎ractice staffs were asked to provide each patient with a written individualized asthma-action plan.” [Pragmatic]

Score: [4]

Flexibility (delivery):

1. “C‎hoices of individual drugs and devices were made according to normal clinical practice and British asthma guidelines.” [Pragmatic]

2. “T‎he protocol discouraged substantial treatment changes between randomization and the 2-month visit.” [Pragmatic]

Score: [4]

Flexibility (adherence):

1. “A‎dherence to an LTRA was better than it was to the other drugs in both trials.” [Pragmatic]

2. “A‎lthough such poor and differential adherence potentially reduces assay sensitivity (particularly when coupled with treatment crossover), thus biasing results toward equivalence, both poor and differential adherence rates are realities of real-world prescribing and thus part of the treatment effect.” [Pragmatic]

Score: [5]

Follow-up:

1. “D‎ata collection and statistical analyses were performed by study personnel who were unaware of the treatment assignments; questionnaire-based data were collected under blinded conditions, and routine practice data (including a history of exacerbations) were extracted with the use of dedicated software.” [Pragmatic]

2. “D‎ata for asthma-related quality of life and asthma control were available over a period of 21 months for 95% and 96% of the patients in the first-line controller and add-on therapy trials, respectively, which are completion rates higher than those in most long-term asthma-therapy trials.” [Pragmatic]

Score: [5]

Primary outcome:

1. “M‎ean improvements over a period of 2 years in both the first-line controller and the add-on therapy trials were substantially greater than the MID for questionnaire scores measuring asthma-related quality of life and asthma control.” [Pragmatic]

2. “F‎or patients receiving an LTRA or an inhaled glucocorticoid as first-line controller therapy, MiniAQLQ scores were equivalent at 2 months, but at 2 years, these scores did not meet our prespecified criterion for equivalence, since the lower boundary of the 95% CI was –0.35.” [Explanatory]

Score: [3]

Primary analysis:

1. “T‎he primary effectiveness analysis was an intention-to-treat analysis of the MiniAQLQ score at 2 months (the primary time point) and at 2 years.” [Pragmatic]

2. “M‎ultiple imputation was used where data were missing.” [Pragmatic]

Score: [4]

Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial (2020), PragQoL

Eligibility:

1. “P‎atient selection criteria were having a diagnosis of moderate-to-severe COPD (a Body mass index, Airflow obstruction, dyspnoea and Exercise capacity [BODE] index score of 3–7) according to international guidelines and having been clinically stable for the previous 4 weeks.” [Score: 4] The eligibility criteria for this trial are relatively broad, allowing for the inclusion of patients with moderate-to-severe COPD who are clinically stable. However, the use of the BODE index score as a criterion narrows the eligibility to a specific subset of patients.

Recruitment:

1. “R‎ecruited patients (recruitment visit, −1) attended an initial 8-week outpatient-based PR programme conducted in each hospital rehabilitation department.” [Score: 4] The recruitment process involved patients attending an outpatient-based PR program, which is similar to usual care. However, the specific details of the recruitment process are not provided in the full text, making it difficult to assess the level of extra effort made to recruit participants.

2. “A‎ll patients gave written informed consent.” [Score: 5] The use of written informed consent suggests that the recruitment process followed standard ethical guidelines and was likely pragmatic in nature.

Setting:

1. “A‎ multicentre open-label pragmatic parallel-group randomized clinical trial involving 13 hospitals.” [Score: 3] The trial was conducted in multiple hospitals, which suggests a more pragmatic approach. However, the specific types of hospitals or settings are not described, making it difficult to fully assess the level of difference from usual care.

Organization:

1. “P‎atients in the IG were asked to continue at home with a similar training schedule to that completed in the hospital.” [Score: 4] The organization of care delivery in the intervention arm was similar to usual care, with patients continuing their training at home. However, the specific resources and provider expertise available in the intervention arm are not described, making it difficult to fully assess the level of difference from usual care.

Flexibility (delivery):

1. “P‎atients in the IG were asked to continue at home with a similar training schedule to that completed in the hospital.” [Score: 4] The intervention arm allowed for flexibility in how the training was delivered, with patients continuing their training at home. However, the specific details of the training protocol and any restrictions or guidelines are not provided, making it difficult to fully assess the level of flexibility.

Flexibility (adherence):

Score: [NA] This domain is not applicable to this trial as there is no mention of adherence issues or measures to improve adherence.

Follow-up:

1. “A‎fter the randomization visit, follow-up appointments were arranged for both groups at 3, 9 and 12 months.” [Score: 4] The follow-up schedule in this trial is similar to usual care, with appointments at regular intervals. However, the specific intensity of measurement and follow-up is not described, making it difficult to fully assess the level of difference from usual care.

Primary outcome:

1. “E‎xercise tolerance (the ability to sustain exercise) was assessed using distance covered in the 6MWT.” [Score: 5] The primary outcome of exercise tolerance is relevant to participants and is a commonly used measure in usual care for COPD patients.

Primary analysis:

1. “A‎ll available data from the randomized patients were used in the mixed models.” [Score: 5] The use of all available data in the analysis suggests a pragmatic approach, using an intention-to-treat analysis with all randomized participants.

Overall, this trial appears to have a pragmatic design, with some domains scoring higher than others. The eligibility criteria, recruitment process, and primary outcome are aligned with usual care, while the setting, organization, and flexibility of delivery show some differences. The flexibility of adherence domain is not applicable, and the level of flexibility in adherence is not described. The follow-up and primary analysis domains align with a pragmatic approach.

Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial. (2019), PragMS

Eligibility:

1. “E‎ighty people with Expanded Disability Status scores of 1 to 6.5 participated in this trial.” [1]

2. “T‎he inclusion criteria were as follows: (1) diagnosed with MS in accordance with the McDonald criteria27; (2) registered at the MS outpatient clinic; (3) living in 1 of 6 selected municipalities; (4) aged 18 years or older; (5) capable of providing signed written informed consent; and (6) EDSS score between 1 and 6.5 (1 = minor disability, 6.5 = able to walk 20 m with or without a walking aid).” [1]

3. No exclusions based on non-compliance, response to treatment, or risk for primary outcome were mentioned. [NA]

Score: [4]

Recruitment:

1. “I‎n August 2015, 1 of the MS nurses at the Department of Neurology, Nordland Hospital Trust in Bodø, Norway, sent out invitation letters with a consent form to 160 persons with MS who were registered at the MS outpatient clinic, had EDSS scores of 0 to 7, and lived in 1 of the 6 municipalities included in the study.” [1]

2. No mention of targeted invitation letters, advertising, or incentives for recruitment. [5]

Score: [3]

Setting:

1. “T‎he GroupCoreDIST intervention was conducted by 6 physical therapists in 6 municipalities in Norway.” [1]

2. No mention of specialized trial or academic centers. [5]

Score: [4]

Organization:

1. “T‎he physical therapists had varied experience (between 7–25 years) and certification (2 had both a master’s degree in neurological physical therapy and were clinical specialists in neurological physical therapy, 1 was a clinical specialist in neurological physical therapy, and 3 were generalists in physical therapy).” [1]

2. No mention of increased staff levels, additional training, or increased resources. [5]

Score: [4]

Flexibility (delivery):

1. “T‎he physical therapists individualized the exercises by tailoring them according to each individual’s symptoms, disability level, and general well-being, and they intensified the exercises by increasing number of repetitions, level of difficulty, and/or by adding motor-cognitive dual tasks as movement quality improved.” [1]

2. No mention of a strict protocol or monitoring. [5]

Score: [4]

Flexibility (adherence):

1. “P‎articipants in the intervention group were encouraged not to seek any physical therapy other than GroupCoreDIST during the 6 weeks of the intervention.” [1]

2. No mention of exclusion based on adherence or measures to improve adherence. [5]

Score: [5]

Follow-up:

1. “A‎ssessments were conducted at baseline and at weeks 7, 18, and 30.” [1]

2. No mention of more frequent or longer visits, unscheduled visits, or extensive data collection. [5]

Score: [5]

Primary outcome:

1. “T‎he TIS-NV, which requires quality of movement and cooperation between body segments in dynamic sitting balance,29 detected a short-term improvement of 19% in the intervention group, which we consider a clinically meaningful change.” [1]

2. No use of surrogate or physiological outcome measures. [5]

Score: [5]

Primary analysis:

1. “A‎ll participants with postintervention test assessment scores were included, although some had missing observations.” [1]

2. No mention of excluding ineligible participants or including only completers or those following the treatment protocol. [5]

Score: [5]

How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study (2020), PragMS

Eligibility:

1. “P‎articipants were included from September 2016 to October 2018, after being invited via seven MS clinics (specified in “Acknowledgements” section) and targeted advertisements sent out via the Danish MS Society. The inclusion criteria were as follows: age > 18, confirmed diagnosis of MS, Expanded Disability Status Scale (EDSS): 2.0–6.5, Six Spot Step Test (SSST) score > 8 seconds or Timed 25-Foot Walk (T25FW) > 5 seconds, relapse-free within the past 8 weeks, and no adjustment of disease-modifying medication or medication that affects gait performance and spasticity within the past 8 weeks. Exclusion criteria were as follows: co-morbidity in terms of cognitive disorders or alcohol abuse (based on clinical judgment), pathologies that did not allow systematic PRT >1 session/week within the last 3 months.” [Score: 3] The inclusion criteria are relatively broad, allowing for a range of participants with MS to be included. However, the exclusion criteria are not clearly defined and may introduce some selection bias.

Recruitment:

1. “P‎articipants were included from September 2016 to October 2018, after being invited via seven MS clinics (specified in “Acknowledgements” section) and targeted advertisements sent out via the Danish MS Society.” [Score: 4] The recruitment methods used in this trial, including invitations through MS clinics and targeted advertisements, are likely to be similar to those used in usual care settings. However, the specific details of the recruitment process are not provided, so a score of 4 is given.

Setting:

1. “T‎his study was designed as a multi-centered, randomized control trial with two intervention groups and a control group (CON).” [Score: 3] The trial was conducted at multiple centers, which may introduce some variation in the setting compared to usual care. However, the specific details of the trial settings are not provided, so a score of 3 is given.

Organisation:

1. “A‎ll training sessions were supervised by physiotherapists who were trained to deliver the intervention.” [Score: 4] The intervention was delivered by trained physiotherapists, which is likely similar to the organization of care in usual care settings. However, the specific details of the organization of care in the intervention arm compared to usual care are not provided, so a score of 4 is given.

Flexibility (delivery):

1. “T‎he BMCT intervention consisted of 20 1-hour training sessions over 10 weeks (two sessions/week). All sessions started with a 10-minute warm-up on a stationary bicycle or treadmill.” [Score: 4] The intervention protocol allows for some flexibility in the delivery, such as the use of stationary bicycle or treadmill for warm-up. However, the specific details of the flexibility in how the intervention is delivered compared to usual care are not provided, so a score of 4 is given.

Flexibility (adherence):

1. “B‎oth BMCT and PRT significantly reduced fatigue impact.” [Score: NA] This domain is not applicable to this trial as there is no compliance issue after consent has been given.

Follow-up:

1. “T‎he follow-up test was performed within 7 days of the last intervention session or after the last day of being on the waitlist.” [Score: 5] The follow-up procedures are similar to usual care, with follow-up assessments conducted shortly after the intervention period or waitlist period. A score of 5 is given.

Primary outcome:

1. “T‎he primary comparisons showed that BMCT, but not PRT, improved T25FW, SSST, and self-perceived gait function when compared to CON.” [Score: 5] The primary outcome measures used in this trial are relevant to participants with MS and are likely to be important outcomes in usual care. The results show that BMCT had a significant effect on these outcomes compared to the control group, while PRT did not. A score of 5 is given.

Primary analysis:

1. “A‎nalyses were carried out as intention-to-treat, where all participants who completed the baseline assessment were included regardless of their adherence to the allocated intervention.” [Score: 5] The primary analysis was conducted on an intention-to-treat basis, which is a pragmatic approach that includes all participants regardless of their adherence to the intervention. A score of 5 is given.

Pragmatic intervention for increasing self-directed exercise behaviour and improving important health outcomes in people with multiple sclerosis: a randomised controlled trial (2014), PragMS

Eligibility:

1. “T‎he inclusion criteria for the trial were clinical diagnosis of MS, as defined by the modified McDonald criteria, with an Expanded Disability Status Scale (EDSS) score of 1.0–6.5, and able to walk a 10-metre distance; aged 18–65 years; clinically stable for at least four weeks prior to entering the study; physically able to participate in exercise three times per week; able to provide written informed consent.” [Score: 4] The eligibility criteria for this trial are relatively broad, including a range of disability levels and age groups. However, there are still some exclusions, such as those who are unable to walk a 10-meter distance or participate in exercise three times per week.

Recruitment:

1. “A‎ total of 120 PwMS were recruited via the Sheffield MS Clinic and flyers/community adverts displayed at the local South Yorkshire MS Society branches.” [Score: 4] The recruitment methods used in this trial include both clinic-based recruitment and community-based advertising. This suggests that some extra effort was made to recruit participants beyond what would be used in usual care, but it is not clear if additional incentives or targeted invitation letters were used.

2. “O‎f 349 potential participants who were assessed for eligibility, 120 (34%) were randomised.” [Score: 3] The recruitment rate of 34% suggests that there may have been some challenges in recruiting participants for this trial. However, without more information on the total number of eligible participants and the reasons for non-participation, it is difficult to fully assess the recruitment efforts.

Setting:

1. “A‎n exercise physiologist supervised the delivery of the intervention but with physiotherapist input during the early stages of the programme.” [Score: 4] The intervention was delivered by an exercise physiologist, which suggests that it was implemented in a specialized setting. However, the involvement of a physiotherapist during the early stages of the program may indicate some flexibility in the setting, potentially allowing for delivery in a more usual care setting.

2. “D‎uring weeks 1–6, participants attended two supervised sessions per week at a university exercise research facility and engaged in one additional self-directed exercise session in their home environment.” [Score: 3] The intervention involved both supervised sessions at a university exercise research facility and self-directed exercise sessions at home. While the university exercise research facility may not be a usual care setting, the inclusion of self-directed exercise at home suggests some flexibility in the setting.

Organisation:

1. “T‎he supervised exercise sessions incorporated cognitive-behavioural techniques to promote long-term participation in physical activity.” [Score: 4] The intervention included cognitive-behavioural techniques, which suggests that some additional resources and training were provided to support participants in their exercise behavior change. However, without more information on the specific resources and training provided, it is difficult to fully assess the level of difference in organization compared to usual care.

Flexibility (delivery):

1. “T‎he prescribed strength training was based on individual functional needs, as assessed by the trial physiotherapist.” [Score: 4] The intervention included individualized strength training based on participants’ functional needs, which suggests some flexibility in how the intervention was delivered. However, without more information on the specific protocols and guidelines used, it is difficult to fully assess the level of flexibility in delivery.

Flexibility (adherence):

Score: [NA] This domain is not applicable to this trial as there is no mention of adherence issues or measures to improve adherence.

Follow-up:

1. “O‎utcomes were assessed at baseline, and at three months (post-intervention) and nine months after randomisation.” [Score: 4] The follow-up period of three and nine months is longer than what would typically be done in usual care. However, without more information on the intensity and frequency of measurement and follow-up, it is difficult to fully assess the level of difference in follow-up compared to usual care.

Primary outcome:

1. “T‎he primary outcome was self-reported exercise behaviour at three months using the Godin Leisure Time Exercise Questionnaire (GLTEQ).” [Score: 4] The primary outcome of self-reported exercise behavior is relevant to participants and is measured using a validated questionnaire. However, without more information on the specific outcomes and their relevance to usual care, it is difficult to fully assess the level of difference in the primary outcome compared to usual care.

Primary analysis:

1. “A‎ll analyses were by intention to treat, whereby participants were analysed in the arm to which they were randomised irrespective of whether they complied with the intervention.” [Score: 5] The primary analysis was conducted on an intention-to-treat basis, which includes all participants regardless of their compliance with the intervention. This approach is consistent with a pragmatic trial design and ensures that the analysis reflects the real-world effectiveness of the intervention.

Computerised cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: external pilot trial (2011), PragMS

Eligibility:

1. “I‎nclusion criteria were: age of 18 years or above; BDI score of at least 14 on two consecutive occasions and no treatment from psychologist, psychotherapist or psychiatrist within the last three months.” [Score: 4]

2. “E‎xclusion criteria were: poor English language skills or cognitive function (score of less than 24 on Mini Mental State Examination [20]); BDI score of at least 29 on two consecutive occasions; active suicidal ideas; current or life-time diagnosis of psychosis, organic mental disorder or substance dependency; Kurtzke Expanded Disability Status Scale (EDSS) score of 8.5 or above [21]).” [Score: 4]

3. “T‎wo participants in each arm were lost to follow-up at 21 weeks post-randomisation.” [Score: 4]

Recruitment:

1. “R‎ecruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar.” [Score: 3]

2. “O‎ur initial aim was to recruit 24 participants between 22 October 2008 and 31 January 2009 (101 days; 7.1 participants/month) with candidates identified by three neurologists working in a single weekly specialist MS clinic (Sheffield Teaching Hospitals NHS Trust).” [Score: 3]

3. “F‎rom the 288 invitation packs given out by Sheffield neurologists in the MS clinic, forms were completed and returned by 63 (21.8%) candidates from which we randomised 13 in 281 days (4.5% recruitment yield), or 1.4 participants per month.” [Score: 3]

Setting:

1. “T‎he MS services in both sites are specific entities and not general neurology clinics.” [Score: 3]

Organisation:

1. “N‎o PCT with whom we worked offered advice or support for defining problems on which to work or applying the CBT model to individual problems.” [Score: 4]

2. “T‎he PCTs delivering CCBT reported that they assumed that patients who were non-adherent and non-contactable beyond two weeks had discontinued treatment and made no further effort to contact them.” [Score: 4]

Flexibility (delivery):

1. “O‎nly one out of the five participating PCTs around the Sheffield centre formally provided any kind of community facility for accessing CCBT; PCT staff warned that clients rarely used the facility and it was closed during the course of the study.” [Score: 3]

Flexibility (adherence):

1. “O‎f the 12 patients in the CCBT arm, 9 (75%) completed at least four CCBT sessions. This translated to a reasonably high compliance rate of CCBT although only six (50%) of the patients in this arm completed all intended eight CCBT sessions.” [Score: 4]

Follow-up:

1. “P‎rimary outcome assessments were available for 21 (88%) participants at 8 weeks from randomisation (or end of treatment if later) and 18 (75%) participants at a further three months’ follow-up.” [Score: 4]

Primary outcome:

1. “T‎he patient reported outcome measure which the participants felt best reflected their concerns was the MSIS-29.” [Score: 4]

Primary analysis:

1. “P‎rimary analysis was an Intention To Treat (ITT) analysis which analysed all 24 participants according to their randomised treatment assignment ignoring non compliance, protocol deviations and withdrawal.” [Score: 5]

Higher satisfaction and adherence with glatiramer acetate 40 mg/mL TIW vs 20 mg/mL QD in RRMS (2019), PragMS

1. Eligibility:

• “K‎ey inclusion criteria permitted the participation of men or women ≥18 years of age with confirmed and documented RRMS diagnosis (as defined by the Revised McDonald criteria) (Polman et al., 2011), Kurtzke Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at the screening visit, and, 30 days prior to randomization, a stable neurological condition, relapse-free status, and no use of any corticosteroid or adrenocorticotropic hormone treatment.”

• “K‎ey exclusion criteria were previous exposure to GA40, a progressive form of MS or neuromyelitis optica, the use of experimental or investigational drugs, participation in clinical drug studies within the 6 months before screening, recent use of immunosuppressive medications or immunoglobulins/monoclonal antibodies, or previous use of alemtuzumab, cladribine, cyclophosphamide, or mitoxantrone.”

The full text provides clear information on the eligibility criteria for the trial, including the specific inclusion and exclusion criteria. The criteria are well-defined and specific to the target population of patients with RRMS. Based on this information, the trial appears to have a relatively explanatory approach with some exclusions, but overall it seems to be pragmatic.

Score: [4]

2. Recruitment:

• “T‎he CONFIDENCE study was a multinational, multicenter, randomized, parallel-group, phase 4, open-label study conducted at 88 study centers in 14 countries (Russia, Poland, Italy, France, Croatia, US [including Puerto Rico], Mexico, Spain, Austria, Turkey, Belgium, Argentina, Germany, and Finland) across different geographic regions.”

• “E‎ligible patients were randomly assigned 1:1 to receive subcutaneous injections of GA40 (n = 431) or GA20 (n = 430). Five scheduled visits at study sites occurred at screening (within 2 weeks prior to baseline), baseline (Month 0), and Months 1, 3, and 6 (end of the core phase). Patients also participated in self-reported, daily at-home MSQ assessments on Days 1 through 7 after the baseline visit.”

The full text provides information on the recruitment process, including the number of study centers and countries involved in the trial. It also mentions the random assignment of eligible patients to the two treatment groups. However, there is no specific information on the recruitment efforts made to engage with patients beyond the standard study visits and assessments.

Score: [3]

3. Setting:

• “T‎he CONFIDENCE study was a multinational, multicenter, randomized, parallel-group, phase 4, open-label study conducted at 88 study centers in 14 countries (Russia, Poland, Italy, France, Croatia, US [including Puerto Rico], Mexico, Spain, Austria, Turkey, Belgium, Argentina, Germany, and Finland) across different geographic regions.”

The full text provides information on the setting of the trial, which involved multiple study centers in 14 different countries. This suggests that the trial was conducted in a variety of settings, including different healthcare systems and regions. However, there is no specific information on how different the trial setting was from the usual care setting.

Score: [3]

4. Organisation:

• “T‎he overall treatment-emergent adverse event (TEAE) profile in both treatment groups was consistent with previous findings (Wolinsky et al., 2015) (Table 2). A significantly lower percentage of patients in the GA40 cohort (8.6%) reported injection-site pruritus than those in the GA20 cohort (13.6%, p = 0.023).”

The full text provides information on the adverse event profile of the two treatment groups, indicating that the overall organization of care delivery in terms of safety monitoring and management was similar between the groups. However, there is no specific information on any additional resources, provider expertise, or changes in care delivery organization in the intervention arm compared to usual care.

Score: [4]

5. Flexibility (delivery):

• No relevant quotes or information provided.

The full text does not provide any information on the flexibility in how the intervention is delivered or how it compares to usual care. Therefore, it is not possible to assess this domain.

Score: [NA]

6. Flexibility (adherence):

• “P‎atients’ adherence to treatment measured at Months 1, 3, and 6 using the MS-TAQ questionnaire showed consistently greater adherence to treatment in patients receiving GA40 compared with those receiving GA20 (Fig. 5).”

The full text provides information on the adherence to treatment measured using the MS-TAQ questionnaire. It indicates that patients receiving GA40 had greater adherence compared to those receiving GA20. This suggests that the trial had a pragmatic approach with no additional measures to improve adherence or exclusion based on adherence.

Score: [5]

7. Follow-up:

• “<span title=‘P‎atients (N = 861) were randomly assigned 1:1 to receive GA20 (n = 430) or GA40 (n = 431) during the core phase. T‎he primary endpoint was patient-reported medication satisfaction using the Medication Satisfaction Questionnaire (MSQ). Secondary endpoints included self-reported convenience perception using the Treatment Satisfaction Questionnaire for Medication-9 convenience component, symptomatic changes (Modified Fatigue Impact Scale, MFIS), and Mental Health Inventory (MHI). Treatment adherence was measured by Multiple Sclerosis Treatment Adherence Questionnaire. Results from the core phase were included.’ style=‘border-bottom: 1px dashed black;’>P‎atients (N = 861) were randomly assigned 1:1 to receive GA20 (n = 430) or GA40 (n = 431) during the core phase. The primary endpoint was patient-reported medication satisfaction using the Medication Satisfaction Questionnaire (MSQ). Secondary endpoints included self-reported convenience perception using the Treatment Satisfaction Questionnaire for Medication-9 convenience component, symptomatic changes (Modified Fatigue Impact Scale, MFIS), and Mental Health Inventory (MHI). Treatment adherence was measured by Multiple Sclerosis Treatment Adherence Questionnaire. Results from the core phase were included.”

The full text provides information on the follow-up period, which lasted for 6 months. It mentions the scheduled visits at study sites at baseline and Months 1, 3, and 6, indicating the intensity of measurement and follow-up during the trial. However, there is no specific information on the likely follow-up in usual care.

Score: [4]

8. Primary outcome:

• “The primary endpoint was patient-reported medication satisfaction using the Medication Satisfaction Questionnaire (MSQ).”

The full text clearly states the primary outcome of the trial, which is patient-reported medication satisfaction using the MSQ. This indicates that the primary outcome is relevant to participants and focuses on their satisfaction with the intervention.

Score: [5]

9. Primary analysis:

• “T‎he intention-to-treat (ITT) analysis set included all randomly assigned participants and were analyzed according to the treatment group to which they were randomly assigned, regardless of which treatment they actually received.”

The full text provides information on the primary analysis, which was based on the intention-to-treat (ITT) analysis set. This indicates that all randomly assigned participants were included in the analysis, regardless of the treatment they actually received. This approach ensures that all data are included in the analysis of the primary outcome.

Score: [5]

Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial (2011), PragMS

Eligibility:

1. “P‎articipants were recruited through a statewide organization providing education and support to people with MS, and a large specialist MS outpatient clinic. To be included, people had to be aged 18 years or more, have a confirmed diagnosis of relapsing–remitting MS, have an Ambulation Index score19 of 2, 3 or 4 (mild to moderate walking disabilities), and have received medical clearance to participate.” [Score: 4] The eligibility criteria for this trial are relatively pragmatic, as they include a broad range of participants with relapsing-remitting MS and mild to moderate walking disabilities. However, the inclusion of participants from specific organizations and the requirement for medical clearance may limit the generalizability of the trial to the broader population of people with MS.

Recruitment:

1. “P‎articipants were recruited through a statewide organization providing education and support to people with MS, and a large specialist MS outpatient clinic. Recruitment information flyers were sent by mail to all potential participants registered on the mailing lists of both organizations.” [Score: 3] The recruitment methods used in this trial involve targeted approaches through specific organizations and mailing lists. While this may increase the likelihood of recruiting eligible participants, it may also introduce selection bias and limit the generalizability of the trial to the broader population of people with MS.

2. “T‎here was good adherence with the training program (92%), compared with the control group’s adherence with the increased attention and social activities program (62%).” [Score: 4] The high adherence rate suggests that the recruitment strategies used in this trial were effective in engaging participants and encouraging their participation in the intervention.

Setting:

1. “T‎he experimental group completed a 10-week (two times per week), PRT program in one of four community gymnasiums in metropolitan and regional areas.” [Score: 4] The use of community gymnasiums for the intervention suggests that the setting of the trial closely resembles usual care settings where people with MS may engage in exercise programs. However, the specific selection of gymnasiums may limit the generalizability of the trial to settings without access to such facilities.

Organization:

1. “P‎articipants in the control group received ‘usual care’ plus a social program.” [Score: 4] The control group received usual care, which suggests that the organization of care delivery in the intervention arm of the trial closely resembles usual care settings for people with MS. However, the addition of a social program may introduce additional resources and expertise that may not be available in usual care settings.

Flexibility (delivery):

1. “T‎he exercises targeted the key lower limb muscles for supporting body weight and for generating and absorbing power during walking.” [Score: 4] The intervention in this trial involved targeted exercises for specific muscle groups, which suggests a relatively pragmatic approach to the delivery of the intervention. However, the specific exercises used may limit the flexibility of the intervention compared to usual care settings where a broader range of exercises may be used.

Flexibility (adherence):

1. “N‎o between-group differences were detected after 10 weeks or 22 weeks for symptoms of muscle stiffness or muscle spasm.” [Score: 5] The trial did not include any specific measures or interventions to improve adherence to the intervention, suggesting a pragmatic approach where no additional efforts were made to improve adherence beyond what would be expected in usual care settings.

Follow-up:

1. “P‎articipants were asked to return to their usual activities and not to continue or commence resistance training until after the follow-up assessment session.” [Score: 4] The follow-up period in this trial involved participants returning to their usual activities, which closely resembles the likely follow-up in usual care settings. However, the specific instructions given to participants may limit the generalizability of the trial to settings where participants may continue or commence resistance training during the follow-up period.

Primary outcome:

1. “A‎t the end of the 10-week program, participants in the PRT group did not significantly increase the distance they walked over 2 min or increase their maximal walking speed compared with the control group.” [Score: 2] The primary outcome measure in this trial, walking performance, was not found to be significantly different between the intervention and control groups. This suggests that the trial may have used outcome measures that are not directly relevant to participants and may not be of obvious importance to them.

Primary analysis:

1. “A‎nalysis of covariance using the baseline measures as covariates was used to determine whether the PRT group improved more than the control group immediately after the 10-week program.” [Score: 5] The primary analysis in this trial used intention-to-treat analysis, including all participants who were allocated and commenced their program, which is a pragmatic approach that includes all available data.

Overall Score: [3.6]

Effects of an individual 12-week community-located “start-to-run” program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis (2019), PragMS

Eligibility:

1. “A‎dults diagnosed with MS were included based on the ability to walk 5 km without rest or use of assistive device.” [1]

2. “E‎xclusion criteria were reports to have run 5 km in the preceding 6 months or a relapse occurring in the preceding 3 months.” [1]

3. “R‎ecruited participants showed only mild walking impairment and likely had high exercise self-efficacy levels as they were willing to engage in an individual community-located running training.” [1]

The eligibility criteria for this trial were relatively strict, as participants had to be able to walk 5 km without rest or use of an assistive device. Additionally, individuals who had run 5 km in the preceding 6 months or experienced a relapse in the preceding 3 months were excluded. The recruitment of participants with mild walking impairment and high exercise self-efficacy suggests a more explanatory approach. Score: [2]

Recruitment:

1. “p‎wMS were assigned to the experimental (EXP) or the “waiting list control” (WLC) group prior to baseline testing.” [1]

2. “P‎articipants had a specific common goal which was to run together on a public event.” [1]

3. “T‎he addition of two group training sessions with direct supervision by the researchers allowed for expert advice and social interaction and peer support.” [1]

The recruitment process involved assigning participants to either the experimental or control group prior to baseline testing. The common goal of running together on a public event and the inclusion of group training sessions with direct supervision suggest a more pragmatic approach to recruitment. Score: [4]

Setting:

1. “p‎wMS were recruited through announcements at REVAL rehabilitation research institute (UHasselt), Flemish MS rehabilitation centers and MS Society, and Move-to-Sport.” [1]

2. “P‎articipants performed their individual training session simultaneously, while being observed by the project dedicated researcher (MSc exercise physiology and PhD) and master students (rehabilitation sciences and physiotherapy).” [1]

The trial was conducted in various settings, including rehabilitation research institutes, MS rehabilitation centers, and MS Society. Additionally, participants performed their individual training sessions simultaneously while being observed by researchers and students. These factors suggest a more pragmatic approach to the setting. Score: [4]

Organisation:

1. “P‎articipants received training instructions by email and were asked to train three times weekly according to a personalized training intensity schedule.” [1]

2. “P‎articipants wore an activity tracker at the waist that registered the intensity of steps per minute.” [1]

3. “P‎articipants were asked to weekly upload data to allow remote supervision of the training adherence by the research assistant.” [1]

The organization of care delivery in the intervention arm involved providing participants with training instructions via email and using activity trackers to monitor their training intensity. Participants were also required to upload data weekly for remote supervision. These aspects suggest a more pragmatic approach to organization. Score: [4]

Flexibility (delivery):

1. “p‎wMS received individualized training instructions during 12 weeks, to be performed in their community aiming to participate in a running event.” [1]

2. “D‎uring the first weeks, training consisted of longer walking bouts, interspersed with short 1′ running bouts. The relative amount of running gradually increased until participants were able to run 5 km without interruption at 12 weeks.” [1]

The intervention involved individualized training instructions that were tailored to each participant’s abilities and aimed to prepare them for a running event. The gradual increase in running volume over the 12-week period suggests a more pragmatic approach to delivery. Score: [5]

Flexibility (adherence):

This domain is not applicable to this trial as there is no compliance issue after consent has been given. Score: [NA]

Follow-up:

1. “P‎articipants were tested at two time points (0 and 12 weeks).” [1]

2. “T‎he EXP group completed a 12-week gradual “start-to-run” program in between time points.” [1]

The trial involved follow-up assessments at two time points: baseline and 12 weeks. The 12-week duration of the intervention suggests a more pragmatic approach to follow-up. Score: [4]

Primary outcome:

1. “T‎he primary outcome measures were physical fitness, walking capacity and perceived ability, functional mobility, and quality of life.” [1]

2. “S‎econdary outcome measures were fatigue, cognitive function, brain volumes, and structural connectivity.” [1]

The primary outcome measures of the trial were physical fitness, walking capacity, functional mobility, and quality of life. These outcomes are relevant to participants and suggest a more pragmatic approach to the primary outcome. Score: [5]

Primary analysis:

1. “I‎ntention-to-treat analysis was performed.” [1]

The trial used an intention-to-treat analysis, which includes all randomized participants in the analysis regardless of adherence to the intervention. This approach suggests a more pragmatic approach to the primary analysis. Score: [5]

Effects of an individual 12-week community-located “start-to-run” program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis (2014), PragMS

Eligibility:

• “P‎articipants were clients seen in the multiple sclerosis clinics at Sutherland-Chan School, in which the study was conducted. Clients were provided with information about the clinic by the local chapter of the Multiple Sclerosis Society, and self selected on that basis.” [1]

• “O‎f the fifteen study participants, all had previously received a diagnosis of multiple sclerosis.” [1]

• “T‎he clients presented to the clinic with a variety of impairments, including some specifically related to the disease process and others that were primarily musculoskeletal in origin.” [1]

The full text provides information about the eligibility criteria for the trial. Participants were clients with a diagnosis of multiple sclerosis who self-selected to participate in the study. The text also mentions that the clients presented with a variety of impairments related to the disease. Based on this information, the trial seems to have a pragmatic approach to eligibility criteria, as it includes a diverse group of participants who are representative of the target population. Score: [4]

Recruitment:

• “C‎lients attending the clinic were interviewed, and their case histories recorded. The research project was explained, and written informed consent was obtained.” [1]

• “T‎he inclusion criterion for the study was a diagnosis of multiple sclerosis, and therefore the spectrum of clinical presentations was broad, as would be expected in this client population.” [1]

The full text does not provide specific information about the recruitment methods used in the trial. However, it mentions that clients attending the clinic were interviewed and provided with information about the research project. Based on this information, it can be inferred that the recruitment process was likely pragmatic, involving the recruitment of participants from the clinic setting. Score: [3]

Setting:

• “P‎articipants were clients seen in the multiple sclerosis clinics at Sutherland-Chan School, in which the study was conducted.” [1]

The full text indicates that the trial was conducted in the multiple sclerosis clinics at Sutherland-Chan School. However, it does not provide information about the specific settings within the clinics or whether the trial was conducted in multiple centers. Based on the available information, it is not possible to determine the score for this domain. Score: [NA]

Organisation:

• “T‎he treatment plans were approved by the clinical teacher in charge.” [1]

• “T‎he teacher also monitored treatment delivery, which involved the application of a variety of techniques appropriate to the client’s needs.” [1]

The full text mentions that the treatment plans were approved by a clinical teacher and that the teacher monitored treatment delivery. This suggests that there was some level of organization and oversight in the delivery of the intervention. However, the text does not provide information about any additional resources, provider expertise, or changes in care delivery organization. Based on the available information, it is not possible to determine the score for this domain. Score: [NA]

Flexibility (delivery):

• “M‎assage therapy is aligned with the wellness paradigm of health and health care, which speaks to a holistic client centered approach to treatment.” [1]

• “A‎ccordingly, if the current research was to conform to the requirements of model fit/ecological validity, it was incumbent on the therapists to construct individualized treatment plans recognizing the importance of the client’s physical, psychological and emotional needs.” [1]

The full text suggests that the delivery of the intervention was flexible and individualized, taking into account the needs of each client. This aligns with a pragmatic approach to the flexibility of intervention delivery. Score: [5]

Flexibility (adherence):

• No relevant quotes.

The full text does not provide information about the flexibility in how participants must adhere to the intervention. Score: [NA]

Follow-up:

• “S‎elf-Efficacy scores were obtained before the first treatment, mid-treatment series, after the last treatment in the series, four weeks after the final treatment and again eight weeks after the final treatment had been received.” [1]

The full text indicates that self-efficacy scores were obtained at multiple time points during and after the treatment series. This suggests that there was a follow-up period to assess the longer-term effects of the intervention. Score: [4]

Primary outcome:

• “S‎elf-Efficacy [SE] was the outcome for the study, measured using the Multiple Sclerosis Self-Efficacy survey [MSSE].” [1]

• “T‎he MSSE survey measures perception, it can be suggested that higher self-efficacy scores reflect improved mood (i.e. reduced depression, anxiety and stress), and a better ability to cope with and adjust to the disease.” [1]

The full text provides information about the primary outcome measure used in the study, which is self-efficacy measured using the MSSE survey. It also suggests that higher self-efficacy scores reflect improved mood and better coping abilities. Based on this information, it can be inferred that the primary outcome is relevant to the participants. Score: [5]

Primary analysis:

• “T‎he data were analyzed on an intention to treat basis, with a focus on the differences between mean MSSE values of the control and intervention groups.” [1]

The full text mentions that the data were analyzed on an intention to treat basis, which suggests that all available data were included in the analysis of the primary outcome. Score: [5]

Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis (2019), PragMS

Eligibility:

1. “K‎ey inclusion criteria were age older than 18 years, a diagnosis of progressive multiple sclerosis (primary or secondary) according to McDonald’s criteria, and a score of 6·5–8·0 on the Expanded Disability Status Scale (EDSS).” [Score: 4] The inclusion criteria are relatively broad, allowing for a wide range of participants with progressive multiple sclerosis to be included in the trial. However, the criteria do specify a specific range on the EDSS scale, which may exclude some individuals with more severe or less severe impairment.

Recruitment:

2. “P‎articipants were recruited through eight health-care organisations, including the UK National Health Service (NHS) Trusts, social enterprises, and third sector multiple sclerosis therapy centres, in two regions (Devon–Cornwall and East Anglia) of the UK.” [Score: 4] The trial recruited participants from a variety of healthcare organizations, including both NHS Trusts and third sector therapy centers. This suggests that efforts were made to engage with a diverse range of patients and recruit participants from different settings.

Setting:

3. “T‎he study was undertaken in eight centres from two regions in the UK.” [Score: 3] The trial was conducted in multiple centers within two regions of the UK. While this suggests some level of diversity in the settings, it is limited to only two regions and may not fully represent the usual care settings for all participants.

Organization:

4. “A‎ll participants received their usual health and social service input throughout the study period.” [Score: 5] The trial allowed participants to continue receiving their usual health and social services, indicating that the organization of care delivery in the intervention arm was similar to usual care.

Flexibility (delivery):

5. “T‎he intervention consisted of two home-based physiotherapy sessions (60 min each) to set up the standing frame programme, supported by six follow-up telephone calls (15 min per call).” [Score: 4] The intervention was delivered in a home-based setting, which is likely more flexible than a clinic or hospital-based setting. However, the intervention did involve a specific number of physiotherapy sessions and follow-up calls, suggesting some level of protocol and structure.

Flexibility (adherence):

6. “P‎articipants were asked to stand for 30 min, three times per week over 20 weeks, and encouraged to continue in the longer term, although no further physiotherapy support was provided.” [Score: 4] Participants were given a specific recommendation for standing frequency and duration, but they were also encouraged to continue standing in the longer term without further support. This suggests a moderate level of flexibility in adherence to the intervention.

Follow-up:

7. “T‎he study had assessor-blinded outcome assessments with use of clinician-rated and patient-rated measures at baseline, 20 weeks, and 36 weeks.” [Score: 5] The trial had regular follow-up assessments at specific time points, which is consistent with usual care practices for monitoring and measuring outcomes in clinical trials.

Primary outcome:

8. “T‎he primary clinical outcome was motor function measured by the Amended Motor Club Assessment (AMCA) score at week 36.” [Score: 5] The primary outcome measure, the AMCA score, is directly relevant to the participants and is a measure of motor function, which is important for individuals with progressive multiple sclerosis.

Primary analysis:

9. “T‎he primary analysis of the primary outcome, AMCA score at 36 weeks, followed a modified intention-to-treat approach, regardless of compliance to the intervention.” [Score: 5] The primary analysis included all participants in the assigned groups, regardless of their compliance with the intervention, which is consistent with a pragmatic approach to analysis.

Overall, the trial appears to have a pragmatic design, with a focus on real-world applicability and relevance to participants. The scores for each domain are as follows:

Eligibility: [4]

Recruitment: [4]

Setting: [3]

Organization: [5]

Flexibility (delivery): [4]

Flexibility (adherence): [4]

Follow-up: [5]

Primary outcome: [5]

Primary analysis: [5]

Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial (2013), PragMS

Eligibility:

• “P‎articipants were randomised in groups of eight to physiotherapist (PT)-led exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86) and they took part in weekly community-based group exercise sessions.” [1]

• “O‎ur study participants were referred to the project by themselves, their care-giver, MSI, chartered physiotherapists, neurologists, general practitioners or clinical nurse specialists.” [2]

• “E‎ligible participants were over 18 years of age and had a diagnosis of MS that was confirmed by a consultant physician or neurologist.” [2]

The full text provides information on the eligibility criteria for the trial. Participants were recruited from various sources and had to meet specific criteria, such as being over 18 years old and having a confirmed diagnosis of MS. The eligibility criteria appear to be pragmatic, as they are similar to those that would be used in usual care. Score: [5]

Recruitment:

• “P‎articipants were randomised in groups of eight to physiotherapist (PT)-led exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86) and they took part in weekly community-based group exercise sessions.” [1]

• “O‎ur study participants were referred to the project by themselves, their care-giver, MSI, chartered physiotherapists, neurologists, general practitioners or clinical nurse specialists.” [2]

The full text does not provide specific information on the recruitment methods used for the trial. However, it mentions that participants were referred to the project by various sources, suggesting that recruitment methods were likely pragmatic and similar to those used in usual care. Score: [4]

Setting:

• “A‎ll interventions took place in groups of eight, for an hour per week, for 10 weeks.” [2]

• “T‎hey were delivered in community centres such as local gyms, hotels and health centres.” [2]

The full text provides information on the setting of the trial. The interventions took place in community settings, such as local gyms, hotels, and health centers. This suggests that the setting was pragmatic and similar to usual care. Score: [5]

Organisation:

• “T‎he PT-led exercise provided was pre-defined.” [2]

• “T‎he FI-led classes were not pre-defined, as the aim was to establish whether these classes were effective when encountered by those with MS in the community.” [2]

• “T‎he yoga intervention was also not predefined.” [2]

The full text provides information on the organization of care delivery in the intervention arms of the trial. The PT-led exercise was pre-defined, suggesting that it may have required additional resources and expertise compared to usual care. The FI-led classes and yoga intervention were not pre-defined, indicating that they may have been more similar to usual care in terms of organization. Score: [3]

Flexibility (delivery):

• “T‎he PT-led exercise provided was pre-defined.” [2]

• “T‎he FI-led classes were not pre-defined, as the aim was to establish whether these classes were effective when encountered by those with MS in the community.” [2]

• “T‎he yoga intervention was also not predefined.” [2]

The full text does not provide specific information on the flexibility in how the intervention was delivered. However, it mentions that the PT-led exercise was pre-defined, suggesting that there may have been less flexibility compared to usual care. The lack of information on the flexibility of the FI-led classes and yoga intervention makes it difficult to assess this domain. Score: [NA]

Flexibility (adherence):

• “A‎ll interventions took place in groups of eight, for an hour per week, for 10 weeks.” [2]

• “P‎articipants were advised to exercise aerobically in the mode of their choice (walking, cycling, swimming or running), with the aim of exercising for 30 minutes, twice a week, at an intensity of 65% of the heart rate max, or a Borg’s rate of perceived exertion of 11–14.” [2]

The full text does not provide specific information on the flexibility in how participants must adhere to the intervention. However, it mentions that participants were advised to exercise aerobically in the mode of their choice, suggesting that there may have been flexibility in adherence similar to usual care. Score: [4]

Follow-up:

• “O‎utcome was assessed at week 24 for the intervention groups only, as it was felt that withholding a potentially beneficial treatment for longer than 12 weeks, from the controls, could be considered unethical.” [2]

The full text provides information on the follow-up period for the trial. Outcome assessment was conducted at week 24 for the intervention groups only, which suggests that the intensity of measurement and follow-up may have been greater than usual care. Score: [2]

Primary outcome:

• “T‎he primary outcome was the Multiple Sclerosis Impact Scale (MSIS) 29v2 physical component, measured before and after the 10-week intervention.” [1]

The full text provides information on the primary outcome measure used in the trial. The MSIS-29v2 physical component is a patient-reported outcome measure that assesses the physical impact of MS. This suggests that the primary outcome was relevant to participants and similar to what would be assessed in usual care. Score: [5]

Primary analysis:

• “A‎ll participants were analysed in the groups to which they were randomised.” [2]

The full text mentions that all participants were analyzed in the groups to which they were randomized, indicating that an intention-to-treat analysis was likely used. This suggests that all data were included in the analysis of the primary outcome, similar to what would be done in usual care. Score: [5]

Is short-term palliative care cost-effective in multiple sclerosis? A randomized phase II trial (2009), PragMS

Eligibility:

1. “P‎atients in South East London who were severely affected by MS were referred by clinicians to the trial.” [Quote 1]

2. “I‎nclusion criteria were patients in South East London, living with MS and deemed (by clinicians) to have one or more of unresolved symptoms, psychosocial concerns, end-of-life issues, progressive illness, or complex needs (i.e., palliative care needs).” [Quote 2]

The full text provides information on the eligibility criteria for the trial. Patients with multiple sclerosis (MS) who were severely affected and had unresolved symptoms, psychosocial concerns, end-of-life issues, progressive illness, or complex needs were included. The trial was conducted in South East London and patients were referred by clinicians. Based on this information, the trial appears to have a pragmatic approach to eligibility criteria, as it includes patients who would typically receive palliative care in usual care settings. Score: [4]

Recruitment:

1. “P‎atients in South East London who were severely affected by MS were referred by clinicians to the trial.” [Quote 1]

2. “E‎ducational seminars informed local health and social care professionals about the PCT.” [Quote 2]

The full text mentions that patients were referred to the trial by clinicians and that educational seminars were conducted to inform healthcare professionals about the palliative care team (PCT). However, there is no information provided on any additional recruitment efforts or strategies used to engage with patients beyond the referral process. Without further details, it is difficult to assess the level of effort made to recruit participants. Score: [NA]

Setting:

1. “P‎atients in South East London who were severely affected by MS were referred by clinicians to the trial.” [Quote 1]

The trial was conducted in South East London, which suggests that the setting of the trial was similar to the usual care setting for patients in that region. Score: [4]

Organisation:

1. “T‎his comprised one part-time consultant in palliative medicine, one part-time clinical nurse specialist, one administrator, and one psychosocial worker, and was based in a large teaching hospital.” [Quote 2]

The full text provides information on the resources and provider expertise available in the intervention arm of the trial. The palliative care team (PCT) consisted of healthcare professionals with expertise in palliative care and the trial was based in a large teaching hospital. This suggests that the trial may have required additional resources and provider expertise compared to usual care. Score: [3]

Flexibility (delivery):

1. “T‎he PCT undertook assessments, suggested ways to improve physical, emotional, social, and other problems, provided specialist welfare benefits advice and bereavement support, and liaised with and acted as a catalyst for local services, both primary and specialist teams.” [Quote 2]

The full text describes the activities of the palliative care team (PCT), which included assessments, providing recommendations for improvement, and offering support and liaison with other services. These activities suggest that there may have been some flexibility in how the intervention was delivered to meet the individual needs of patients. Score: [3]

Flexibility (adherence):

No information is provided in the full text to assess the flexibility in how participants must adhere to the intervention. Score: [NA]

Follow-up:

1. “D‎ata were collected at baseline, 6, 12, 18, and 26 weeks on use of services, patient symptoms, other outcomes, and caregiver burden.” [Quote 1]

The full text mentions the follow-up periods for data collection, which were conducted at multiple time points up to 26 weeks. This suggests that the intensity of measurement and follow-up in the trial may have been more frequent and longer than usual care. Score: [2]

Primary outcome:

1. “A‎t 12 weeks, caregiver burden was 4.47 points lower (95% confidence interval [CI]: 1.05–7.89) in the fast track compared to the control group.” [Quote 2]

The primary outcome of the trial was caregiver burden, which is relevant to the participants and their caregivers. The trial focused on improving the well-being of patients and their caregivers, which suggests a pragmatic approach to the primary outcome. Score: [5]

Primary analysis:

1. “W‎e planned an intention-to-treat analysis, irrespective of whether patients were assessed as having palliative care needs or the nature of contact with the PCT.” [Quote 2]

The full text mentions that an intention-to-treat analysis was planned, which indicates that all data, including data from ineligible post-randomization participants, were included in the analysis of the primary outcome. This approach aligns with a pragmatic analysis that includes all available data. Score: [5]

The effects of a 12-week leisure centre-based, group exercise intervention for people moderately affected with multiple sclerosis: a randomized controlled pilot study (2012), PragMS

Eligibility:

1. “P‎articipants were recruited from this register. Participants had a confirmed diagnosis of multiple sclerosis, an Extended Disability Status Scale33 score of 5 (ambulatory without aid or rest for about 200 m) to 6.5 (constant bilateral assistance required to walk about 20 m without resting), stable rehabilitation and drug therapy for 30 days before entry into the study, cognitive scores of over 24 on the Mini-Mental State Examination34 and access to the intervention sites using their own or public transport.” [Score: 4] The eligibility criteria for this trial are moderately pragmatic. They include specific inclusion criteria related to the severity of multiple sclerosis and exclude individuals with recent exacerbations or medical conditions that may preclude them from participating. However, the criteria are not overly restrictive and are likely to include a representative sample of individuals with multiple sclerosis.

Recruitment:

1. “O‎f the 873 patients on the clinical register for multiple sclerosis 159 patients were deemed suitable for the study. These people were sent invitation letters and participant information sheets. Forty-three potential participants expressed an interest in participating.” [Score: 4] The recruitment methods used in this trial are moderately pragmatic. The study recruited participants from a clinical register and sent invitation letters to eligible individuals. While this approach may have introduced some selection bias, it is likely to be similar to how participants would be recruited in usual care settings.

Setting:

1. “T‎he intervention took place at two different geographical locations (Site A and Site B).” [Score: 4] The setting of this trial is moderately pragmatic. The intervention was conducted in community leisure centers, which are likely to be similar to the usual care settings where individuals with multiple sclerosis would receive exercise interventions.

Organization:

1. “P‎articipants assigned to the intervention group attended a leisure centre-based exercise class, twice weekly for 12 weeks. Each group was led by two instructors (one physiotherapist and one fitness instructor).” [Score: 4] The organization of care delivery in this trial is moderately pragmatic. The intervention was delivered by a team of instructors, including a physiotherapist and a fitness instructor, which is likely to be similar to the usual care setting where individuals with multiple sclerosis would receive exercise interventions.

Flexibility (delivery):

1. “P‎articipants completed a circuit of 8–12 different exercises for 1 minute each, having a rest (of a minimum of 1 minute) before moving to the next exercise. Not all exercises were performed at all classes, and in week 9 a fifth level of difficulty was added to some of the exercises to encourage progress.” [Score: 4] The flexibility in how the intervention is delivered in this trial is moderately pragmatic. The exercise program included a variety of exercises and allowed participants to progress in difficulty over time. This approach is likely to be similar to the flexibility in how exercise interventions are delivered in usual care settings.

Flexibility (adherence):

1. “P‎articipants assigned to the control group were advised to continue their usual routine, seeking any healthcare as required. They were asked to avoid beginning any new exercise regime for the 12 weeks of the study.” [Score: 5] The flexibility in how participants must adhere to the intervention in this trial is very pragmatic. The control group was not required to adhere to any specific exercise regimen and were allowed to continue their usual routine. This approach is similar to usual care where individuals with multiple sclerosis may or may not engage in exercise.

Follow-up:

1. “O‎utcome measures were carried out within the local hospital’s rehabilitation unit. They were taken at baseline, after 8 and 12 weeks of the intervention period (i.e. either the exercise class or usual care).” [Score: 4] The intensity of measurement and follow-up in this trial is moderately pragmatic. Outcome measures were collected at baseline, after 8 weeks, and after 12 weeks, which is likely to be similar to the follow-up in usual care settings.

Primary outcome:

1. “F‎or the primary outcome measure, the Timed 25-Foot Walk Test, the ANOVA results demonstrated no statistically significant difference over time.” [Score: 2] The primary outcome measure in this trial is more explanatory than pragmatic. The Timed 25-Foot Walk Test is a physiological outcome that may not be directly relevant to participants. Additionally, the lack of statistically significant difference over time suggests that the outcome may not be of obvious importance to participants.

Primary analysis:

1. “D‎ata were analysed using a univariate general linear model analysis of variance (ANOVA) which allowed for missing data, possible differences over time (baseline, week 8 and week 12) and possible differences between groups (intervention and control) to be assessed.” [Score: 4] The primary analysis in this trial is moderately pragmatic. The analysis included all available data and accounted for possible differences over time and between groups.

Overall score: [3.6]

Evaluation of an integrated multidisciplinary approach in multiple sclerosis care: A prospective, randomized, controlled study (2015), PragMS

Eligibility:

1. “I‎nclusion criteria were: having MS (MacDonald criteria); being able to complete a questionnaire; and being in need for a multidisciplinary approach, defined by the requirement, in addition to the neurology specialist, of at least two different medical (rehabilitation specialist, neuro-urology specialist, psychiatrist) or allied health professionals (physiotherapist, occupational therapist, social worker, psychologist, and neuropsychologist).” [Score: 4] The inclusion criteria for this trial are relatively broad and include patients with MS who require a multidisciplinary approach. However, the specific requirements for the multidisciplinary approach are not clearly defined, which may limit the generalizability of the trial to other settings.

Recruitment:

1. “M‎S patients from the outpatient clinic of the Neurology Department of Pitié-Salpêtrière Hospital were prospectively enrolled in the study between March 2010 and July 2012.” [Score: 4] The trial recruited patients from a specific outpatient clinic, which may limit the generalizability of the trial to other settings. However, the recruitment process itself does not appear to involve any additional effort beyond usual care.

2. “S‎igned informed consent was obtained for each patient at inclusion.” [Score: 5] The trial used standard informed consent procedures, which is consistent with usual care.

Setting:

1. “T‎his is a prospective, randomized, controlled, monocentric clinical trial in MS patients.” [Score: 1] The trial was conducted at a single center, which may limit the generalizability of the trial to other settings. It is not clear if this single center is a specialized trial or academic center, which would further limit generalizability.

Organisation:

1. “F‎or patients in the IMD group, the multidisciplinary integrated outpatient clinic was planned at our MS clinic within a maximum three-month period after inclusion.” [Score: 4] The trial used a multidisciplinary integrated outpatient clinic, which suggests that there may be some differences in the organization of care delivery compared to usual care. However, the specific differences in resources, provider expertise, and organization of care delivery are not clearly described.

2. “T‎he study protocol was approved by the coordinator of our local (Pitié-Salpêtrière Hospital) ethics committee, and formal review by the committee was judged unnecessary.” [Score: 5] The trial followed standard ethical approval procedures, which is consistent with usual care.

Flexibility (delivery):

1. “D‎epending on their needs, evaluated during the inclusion visit and re-evaluated during the multidisciplinary visit, patients were seen by different MS specialists and allied health professionals.” [Score: 4] The trial allowed for flexibility in how the intervention was delivered, with patients being seen by different specialists and allied health professionals based on their individual needs. However, the specific details of the flexibility in the intervention delivery are not clearly described.

Flexibility (adherence):

Score: [NA] This domain is not applicable to this trial as there is no mention of adherence issues or measures to improve adherence.

Follow-up:

1. “P‎rimary and secondary outcomes were assessed at inclusion, and after six (M6) and 12 (M12) months.” [Score: 5] The trial followed a standard follow-up schedule, with assessments at baseline, 6 months, and 12 months, which is consistent with usual care. There is no indication of more frequent or extensive follow-up compared to usual care.

Primary outcome:

1. “T‎he primary outcome was the change in QoL from inclusion to M6, assessed by the Multiple Sclerosis Impact Scale (MSIS-29) self-questionnaire.” [Score: 5] The primary outcome of the trial is directly relevant to the participants, as it measures the impact of the intervention on their quality of life.

Primary analysis:

1. “A‎ll analyses were performed with the SAS software version 9.2 (SAS Institute, Cary, NC, USA).” [Score: 5] The trial used intention-to-treat analysis with all available data, which is consistent with a pragmatic approach to the primary analysis.

Web-based physiotherapy for people moderately affected with Multiple Sclerosis; quantitative and qualitative data from a randomized, controlled pilot study (2014), PragMS

Eligibility:

1. “T‎hirty community dwelling adults moderately affected by MS (Expanded Disability Status Scale 5-6.5).” - This quote indicates that the trial included participants who were moderately affected by MS, which is similar to the population that would receive this intervention in usual care. [Score: 4]

Recruitment:

1. “L‎etters were sent to 138 patients from the Multiple Sclerosis Service database, thought to be suitable for the study, inviting them to participate.” - This quote suggests that participants were recruited from a database of patients who were thought to be suitable for the study, which may not be representative of the usual care setting. [Score: 2]

Setting:

1. “R‎ehabilitation centre and participants’ homes.” - This quote indicates that the trial took place in a rehabilitation center and participants’ homes, which may not be the usual care setting. [Score: 2]

Organisation:

1. “T‎he website, which was used to deliver the intervention, was developed in collaboration with a patient steering group and incorporating recommendations from the MS Society accessibility policy and advice from the Scottish Accessible Information Forum.” - This quote suggests that the intervention was developed in collaboration with patient input and incorporated recommendations from relevant organizations, which may not be representative of usual care. [Score: 2]

Flexibility (delivery):

1. “P‎articipants were given unique log-in details to view their own, online personalised exercise programme. This was a pragmatic study with the content of the web-based programme being similar to the content if it had been delivered face-to-face.” - This quote indicates that the intervention was delivered online and participants had access to their own personalized exercise program, which may not be as flexible as usual care. [Score: 3]

Flexibility (adherence):

1. “P‎articipants were advised to undertake the exercise programme a minimum of twice a week and to complete their online exercise diary which was seen remotely by the physiotherapist.” - This quote suggests that participants were encouraged to adhere to the exercise program and their adherence was monitored remotely, which may not be representative of usual care. [Score: 2]

Follow-up:

1. “O‎utcome measures were recorded at baseline and at the end of the intervention period (week 13).” - This quote indicates that follow-up measurements were taken at baseline and at the end of the 12-week intervention period, which may not be as intensive as usual care. [Score: 3]

Primary outcome:

1. “T‎he primary outcome measure, the timed 25ft walk,14 has good reliability and validity in the MS population.” - This quote suggests that the primary outcome measure is relevant to participants with MS. [Score: 5]

Primary analysis:

1. “A‎ll analysis was performed on SPSS v20 with power calculations for a future fully powered trial being estimated using nQuery v7.” - This quote indicates that all available data were included in the analysis of the primary outcome. [Score: 5]

Overall, the trial appears to be more explanatory than pragmatic. The scores for each domain are as follows:

Eligibility: [4]

Recruitment: [2]

Setting: [2]

Organisation: [2]

Flexibility (delivery): [3]

Flexibility (adherence): [2]

Follow-up: [3]

Primary outcome: [5]

Primary analysis: [5]

Randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis (2018), PragMS

Eligibility:

1. “P‎articipants were non-institutionalized adults (age ⩾ 18 years) with severe MS and their primary carers. Other patient inclusion criteria were primary or secondary progressive MS,1,13 Expanded Disability Status Scale (EDSS) score ⩾ 8.0,14 complex symptoms,15 and ⩾2 unmet care needs.16 The carer (a family member, relative, or friend of the patient) was his or her next of kin and was designated by the patient except for patients with severe cognitive compromise.” [Score: 4] The eligibility criteria for this trial are fairly pragmatic, as they include a broad range of patients with severe MS and their primary carers. However, the exclusion of patients with severe cognitive compromise may limit the generalizability of the results to this population.

Recruitment:

1. “P‎articipants were non-institutionalized adults (age ⩾ 18 years) with severe MS and their primary carers.” [Score: 4] The recruitment strategy for this trial appears to be fairly pragmatic, as it targets non-institutionalized adults with severe MS and their primary carers. However, the full text does not provide specific details about the recruitment process, such as whether participants were recruited from multiple sites or how they were identified and approached.

Setting:

1. “I‎n this randomized, examiner-blind, controlled study, we recruited patients from three Italian centers.” [Score: 3] The trial was conducted at three Italian centers, which suggests that the setting may be somewhat explanatory. However, without further information about the characteristics of these centers and how they compare to usual care settings, it is difficult to make a definitive assessment.

Organisation:

1. “B‎ased on the principles of PC,17 each center had a HPA team consisting of a physician (neurologist or physiatrist), a nurse (case manager and team leader), a psychologist, and a social worker.” [Score: 4] The organization of care delivery in the intervention arm of the trial appears to be fairly pragmatic, as it involves a multi-professional team that is consistent with usual care for palliative care. However, the full text does not provide specific details about any additional resources, provider expertise, or changes in care delivery that may be different from usual care.

Flexibility (delivery):

1. “A‎fter a comprehensive assessment of the dyad needs based on direct observation and on visit 1 information (available via the eCRF), the HPA team defined the contents of the intervention, involving the dyad and the patient caring physician (the intervention was not intended to replace existing services).” [Score: 4] The flexibility in how the intervention is delivered appears to be fairly pragmatic, as it is based on a comprehensive assessment of the dyad’s needs and involves collaboration with the patient’s physician. However, the full text does not provide specific details about any strict protocols or measures to improve compliance that may be different from usual care.

Flexibility (adherence):

1. “I‎n the event of emergencies, dyads contacted the patient caring physician or emergency medical services.” [Score: 5] The flexibility in how participants must adhere to the intervention appears to be very pragmatic, as there are no specific requirements for adherence or measures to improve adherence mentioned in the full text. This domain may not be applicable to this trial, as there is no mention of compliance issues or specific interventions to improve adherence.

Follow-up:

1. “A‎ blind examiner assessed dyads at baseline, 3 months, and 6 months.” [Score: 4] The intensity of measurement and follow-up of participants in the trial appears to be fairly pragmatic, as it involves assessments at baseline, 3 months, and 6 months. However, the full text does not provide specific details about the frequency or duration of these assessments compared to usual care.

Primary outcome:

1. “P‎rimary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients).” [Score: 4] The primary outcome measures for this trial appear to be fairly pragmatic, as they include patient-reported outcomes that are relevant to participants with severe MS. However, the exclusion of severely cognitively compromised patients from the SEIQoL-DW assessment may limit the generalizability of the results to this population.

Primary analysis:

1. “A‎ll randomly assigned patients were included in the main intention-to-treat analysis, provided that at least one contact with the team occurred (HPA group).” [Score: 5] The primary analysis of the trial appears to be very pragmatic, as it includes all randomly assigned patients in the intention-to-treat analysis. There is no mention of any exclusions or restrictions on the data included in the analysis.

Overall, the trial appears to have a fairly pragmatic design, with some domains leaning more towards the explanatory end of the spectrum. The eligibility criteria, recruitment strategy, and primary outcome measures are all fairly pragmatic, while the setting, organization of care delivery, and flexibility in delivery are somewhat explanatory. The flexibility in adherence and the intensity of follow-up appear to be very pragmatic.

A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis (2013), PragMS

Eligibility:

1. “T‎he main inclusion criteria were: (1) clinically definite MS diagnosis, (2) fatigue impacting on daily life (Fatigue Severity Scale total score >4)16 and (3) ambulatory. The main exclusion criteria were: (1) having taken part in a fatigue programme in the last year, (2) cognitive impairments, (3) a relapse in the previous 3 months or (4) having started treatment with disease modifying or antidepressant drugs within the previous 3 months.” [Score: 4]

Recruitment:

1. “P‎articipants were recruited in three UK centres (Poole, Bristol, Southampton/Portsmouth) from primary or secondary care, or via MS Society newsletters/websites.” [Score: 4]

Setting:

1. “F‎ACETS was delivered in hotel meeting-room facilities, with the exception of one centre, where it was held in a rehabilitation hospital.” [Score: 3]

Organisation:

1. “F‎acilitators were all qualified to a senior/advanced level (in the UK minimum of a Band 7 on the NHS Agenda for Change (AfC) grading structure).17 Facilitators were trained to deliver the intervention at 1-day workshops and psychological advice and debriefing were available for facilitators throughout the trial.” [Score: 4]

Flexibility (delivery):

1. “T‎he manualised group-based FACETS programme is described elsewhere13 and is based upon a conceptual framework integrating elements from cognitive behavioural, social-cognitive, energy effectiveness, self-management and self-efficacy theories.” [Score: 4]

Flexibility (adherence):

1. “P‎articipants receiving the intervention continued to have access to services available as part of their usual local care.” [Score: 5]

Follow-up:

1. “F‎or those allocated to the FACETS arm, outcomes were measured 1 week (baseline) before the start of FACETS and 1 month (follow-up 1) and 4 months (follow-up 2) after the final session.” [Score: 4]

Primary outcome:

1. “T‎here were statistically significantly greater improvements in fatigue self-efficacy in the FACETS arm at follow-up 1 and 2 compared with the CLP arm.” [Score: 4]

Primary analysis:

1. “T‎he main analysis was intention-to-treat but we also conducted a ‘per protocol’ analysis (excluding participants who attended fewer than four FACETS sessions).” [Score: 4]

Improving Health of People With Multiple Sclerosis From a Multicenter Randomized Controlled Study in Parallel Groups: Preliminary Results on the Efficacy of a Mindfulness Intervention and Intention Implementation Associated With a Physical Activity Program (2021), PragMS

Eligibility:

1. “I‎nclusion criteria for the study included (1) a diagnosis of MS, (2) not currently engaged in rehabilitation, therapy or PA program and able to undertake PA without risk-factors (3) aged between 18 and 65 (4) able to give informed consent and to understand French.” [1]

2. “W‎e excluded those who were receiving drug treatment for fatigue started less than three months ago or acute hospital or nursing home, those who were having psychiatric disorders.” [1]

The full text provides clear information on the eligibility criteria for the study, including the inclusion and exclusion criteria. The criteria are specific and relevant to the target population of people with MS. Based on this information, the trial appears to have a pragmatic approach to eligibility.

Score: [4]

Recruitment:

1. “P‎articipants were recruited from two hospitals in the Parisian region, in France receiving outpatient services for MS at a regional medical center.” [1]

2. “P‎articipants were approached by the study coordinator and asked if they would be willing to participate in it.” [1]

The full text provides limited information on the recruitment process. It mentions that participants were recruited from two hospitals and approached by the study coordinator, but it does not provide details on any additional efforts made to recruit participants or any specific recruitment strategies used. Based on the available information, it is difficult to determine the level of effort made to recruit participants beyond what would be used in usual care.

Score: [3]

Setting:

1. “T‎his clinical and multicentric trial took place from July 2017 to January 2020, in two hospitals in the Parisian Region, France (Hospitals – CHI Poissy St Germain-en-Laye and R. Poincaré, Garches).” [1]

The full text provides information on the setting of the trial, which took place in two hospitals in the Parisian Region. However, it does not provide any details on how the settings of the trial compare to usual care settings. Without this information, it is difficult to assess the level of difference between the trial setting and usual care settings.

Score: [NA]

Organisation:

1. “T‎he PA program was manualized and available as a booklet.” [1]

2. “T‎he PA program was delivered by a neurologist and a specialist in physical medicine and rehabilitation.” [1]

The full text provides limited information on the organization of care delivery in the intervention arm of the trial. It mentions that the PA program was manualized and delivered by a neurologist and a specialist in physical medicine and rehabilitation. However, it does not provide details on any additional resources, provider expertise, or changes in care delivery compared to usual care. Based on the available information, it is difficult to assess the level of difference in organization between the intervention arm and usual care.

Score: [3]

Flexibility (delivery):

1. “P‎articipants in the control group were not guided to develop if-then plans and they did not receive any mindfulness training, however, they received the same PA program over a period of eight weeks.” [1]

The full text indicates that the control group did not receive any additional guidance or training beyond the PA program. This suggests that the delivery of the intervention in the control group was similar to usual care, with no additional flexibility or specific protocol. However, the text does not provide information on the flexibility in how the intervention was delivered in the intervention groups compared to usual care.

Score: [NA]

Flexibility (adherence):

1. “P‎articipants were asked to develop a concrete if-then plan (the “if” component followed by the “then” component) once a week and share them through TailorBuilder app.” [1]

The full text provides information on the flexibility in how participants were asked to adhere to the intervention. They were asked to develop if-then plans once a week and share them through an app. This suggests that there was some flexibility in how participants were expected to adhere to the intervention. However, the text does not provide information on any measures to improve adherence or any exclusions based on adherence.

Score: [4]

Follow-up:

1. “T‎he primary outcomes, fatigue, mobility, and quality of life, were examined at baseline prior to randomization, and then 8-weeks after the intervention (following the online intervention).” [1]

The full text provides information on the follow-up period, which was 8 weeks after the intervention. This suggests that the intensity of measurement and follow-up in the trial was similar to usual care, with no additional visits or measurements beyond what would typically be done. However, the text does not provide details on the specific measurements and follow-up procedures used.

Score: [4]

Primary outcome:

1. “T‎he primary outcomes, fatigue, mobility, and quality of life, were examined at baseline prior to randomization, and then 8-weeks after the intervention (following the online intervention).” [1]

The full text provides information on the primary outcomes of the trial, which include fatigue, mobility, and quality of life. These outcomes are relevant to participants and are commonly assessed in MS trials. However, the text does not provide information on any use of surrogate or physiological outcomes, central adjudication, or assessment expertise that is not available in usual care.

Score: [5]

Primary analysis:

1. “T‎he Wilcoxon signed rank test showed a statistically significant difference in change scores across the three groups for the MSIS-29 physical component.” [1]

The full text provides limited information on the primary analysis of the trial. It mentions the use of the Wilcoxon signed rank test to assess differences in change scores across the three groups for the MSIS-29 physical component. However, it does not provide information on the inclusion of all available data in the analysis or any exclusions or restrictions in the analysis.

Score: [NA]

Hippotherapy for patients with multiple sclerosis: A multicenter randomized controlled trial (MS-HIPPO) (2018), PragMS

Eligibility:

• “M‎S patients older than 18 years who had a confirmed MS with spasticity of the lower limbs and an Expanded Disability Status Scale (EDSS) between 4 and 6.5 were eligible for inclusion.” [1]

• “P‎atients who had received hippotherapy within the last 12 months, a body weight over 90 kg, no balance while sitting, and acute exacerbation during the 4-week period before start of the therapy were excluded.” [1]

• “A‎ planned start of treatment with new anti-spastic drugs or other medications that may have an influence on the assessed outcomes also resulted in exclusion.” [1]

The eligibility criteria for this trial appear to be relatively pragmatic. The inclusion criteria are specific to MS patients with spasticity of the lower limbs and an EDSS score between 4 and 6.5. The exclusion criteria are reasonable and do not appear to overly restrict the participant population. Overall, the trial seems to have a pragmatic approach to participant eligibility.

Score: [4]

Recruitment:

• “A‎ total of 70 adults with MS were recruited in five German centers and randomly allocated to the intervention group (12 weeks of hippotherapy) or the control group.” [1]

The recruitment process is not described in detail in the full text. However, it is mentioned that 70 adults with MS were recruited in five German centers. The recruitment process does not appear to involve any additional efforts beyond what would be used in usual care. Therefore, it can be considered relatively pragmatic.

Score: [4]

Setting:

• “T‎he study was conducted at five sites in Germany, all of which have hippotherapy experience as stipulated by the rules of the German Consortium for Therapeutic Riding.” [1]

The trial was conducted at five sites in Germany, which suggests a relatively pragmatic choice of settings. However, it is not clear if these sites are representative of usual care settings for MS patients. Without further information, it is difficult to fully assess the setting domain.

Score: [NA]

Organisation:

• “P‎atients in the control group continued their previous therapy. Over the study period, symptomatic drug treatment, immunotherapy, and physiotherapy were kept unchanged in both groups.” [1]

The trial appears to have a pragmatic approach to the organization of care delivery. The control group continued their previous therapy, and there were no changes to symptomatic drug treatment, immunotherapy, and physiotherapy in either group. This suggests that the trial used resources and care delivery methods that are consistent with usual care.

Score: [5]

Flexibility (delivery):

• “P‎atients of the intervention group received hippotherapy (as defined by the regulations for hippotherapy of the Deutsches Kuratorium für Therapeutisches Reiten e.V. (DKThR)) once a week for 12 weeks as an add-on therapy to their standard care, which remained unchanged.” [1]

The intervention group received hippotherapy once a week for 12 weeks as an add-on therapy to their standard care, which remained unchanged. This suggests a relatively pragmatic approach to the delivery of the intervention, as it aligns with usual care practices.

Score: [5]

Flexibility (adherence):

• This domain is not applicable to this trial as there is no mention of adherence issues or measures to improve adherence.

Score: [NA]

Follow-up:

• “E‎xaminations and questionnaires were completed prior to the first hippotherapy session (baseline), after 6–7 weeks (interim assessment) and after 12 weeks (final assessment).” [1]

The trial had follow-up assessments at baseline, after 6-7 weeks, and after 12 weeks. This suggests a pragmatic approach to the intensity of measurement and follow-up, as it aligns with usual care practices.

Score: [5]

Primary outcome:

• “P‎rimary outcome was the change in the Berg Balance Scale (BBS) after 12 weeks.” [1]

The primary outcome of the trial, the change in the Berg Balance Scale after 12 weeks, appears to be relevant to participants. The BBS is a measure of balance function, which is likely important to MS patients. Therefore, the trial can be considered relatively pragmatic in terms of the primary outcome.

Score: [5]

Primary analysis:

• “A‎nalyses were based on the modified intention-to-treat set (modified ITT). This set encompasses all randomized patients with valid baseline assessment.” [1]

The trial used a modified intention-to-treat analysis, which includes all randomized patients with valid baseline assessment. This suggests a pragmatic approach to the analysis of the primary outcome, as it includes all available data.

Score: [5]

Center-Based Group and Home-Based Individual Exercise Programs Have Similar Impacts on Gait and Balance in People With Multiple Sclerosis: A Randomized Trial (2021), PragMS

Eligibility:

1. “I‎nclusion criteria were the following: diagnosis of MS made by a neurologist, able to walk 10 meters with or without an aid within 2 minutes, no relapse of their MS in the past 4 weeks, and no other neurological or orthopedic condition that would affect their function.” [1]

2. “E‎ligible participants were excluded from the study if they were already engaged in a formal exercise program lasting >30 minutes twice per week, experienced an exacerbation within the past 4 weeks, had their MS immunomodulation medications altered in the previous 4 weeks or during the trial period, or declined to be randomly allocated.” [1]

The eligibility criteria for this trial appear to be relatively pragmatic. The inclusion criteria are straightforward and align with typical characteristics of people with MS who would be eligible for this type of intervention. The exclusion criteria are also reasonable and do not overly restrict the population that would receive this intervention in usual care. Score: [4]

Recruitment:

1. “C‎ommunity dwelling people with MS were recruited through the Multiple Sclerosis Society of New South Wales and South Australia.” [1]

The recruitment strategy for this trial involved recruiting participants from the community through a well-established organization that supports people with MS. This approach is likely to be similar to how participants would be recruited in usual care. Score: [5]

Setting:

1. “T‎he group program was conducted at a local community center and included four to six participants per class.” [1]

2. “H‎ome exercise participants were provided with one center-based physiotherapist-led session at the commencement of the intervention period for training, and telephone support by a physiotherapist to discuss their program every 2 weeks.” [1]

The trial was conducted in both a community center and participants’ homes, which reflects a pragmatic approach to the setting. The use of a community center allows for group-based exercise sessions, which may be more accessible and cost-effective for participants. The home-based intervention also aligns with usual care, as many individuals with MS may prefer to exercise at home. Score: [4]

Organization:

1. “T‎he group program was conducted at a local community center and included four to six participants per class. Groups were led by a physiotherapist employed by the Multiple Sclerosis Society who received training to ensure a standard approach to intervention, intensity, and progression.” [1]

2. “H‎ome exercise participants were provided with one center-based physiotherapist-led session at the commencement of the intervention period for training, and telephone support by a physiotherapist to discuss their program every 2 weeks.” [1]

The organization of care delivery in both the group and home-based interventions appears to be pragmatic. The group program was led by a physiotherapist who received training to ensure consistency in the intervention. The home-based participants also received initial training and ongoing support from a physiotherapist. These approaches align with usual care and do not involve significant increases in resources or staff levels. Score: [4]

Flexibility (delivery):

1. “T‎he exercise program for both groups included two, 60-minute sessions per week, held at least 2 days apart for 8 weeks.” [1]

2. “E‎xercises were aimed at improving gait speed, endurance, and balance. They were individualized, specific, progressed in load, and performed at a moderate to high intensity.” [1]

The delivery of the intervention appears to be pragmatic in terms of flexibility. The exercise program was individualized and progressed in load, allowing for adaptation to each participant’s needs. The frequency and duration of the sessions are also reasonable and align with what would be feasible in usual care. Score: [4]

Flexibility (adherence):

This domain is not applicable to this trial as there is no compliance issue after consent has been given. Score: [NA]

Follow-up:

1. “P‎articipants attended a local community center to complete all assessments at pre-intervention (week 0), post-intervention (week 8), and at follow-up (week 16).” [1]

The follow-up assessments were conducted at a local community center, which is likely similar to the setting where participants would receive usual care. The timing of the assessments (pre-intervention, post-intervention, and follow-up) also aligns with what would be feasible in usual care. Score: [5]

Primary outcome:

1. “T‎he primary outcome was gait speed (10-meter walk test).” [1]

The primary outcome of gait speed is relevant to participants with MS as it directly measures their mobility and functional ability. This outcome is of obvious importance to participants and aligns with what would be assessed in usual care. Score: [5]

Primary analysis:

1. “D‎ata were analyzed according to the intention-to-treat principle.” [1]

The analysis of the primary outcome was conducted according to the intention-to-treat principle, which is a pragmatic approach that includes all randomized participants and reflects how the intervention would be evaluated in usual care. Score: [5]

The effects of acupressure on labor pains during child birth: randomized clinical trial1 (2016), PragQoL

Eligibility:

1. “W‎e selected 156 pregnant women in their ≥ 37 week/s, who had cervical dilations of ≥ 4 cm and with two or more contractions in 10 minutes.” [Quote 1]

2. “T‎hose with the following were excluded: serious preeclampsia, placenta previa, immediate indication of cesarean, dilations at ≥ 8 cm and those that used analgesics for less than six hours from the study admission time.” [Quote 2]

3. “T‎he size of the sample was estimated through considering the proposed calculation method for the non-paired 14 t test.” [Quote 3]

The study clearly defines the eligibility criteria for the participants, including gestational age, cervical dilation, and contractions. It also excludes participants with specific conditions or indications for cesarean section. The sample size calculation is mentioned, indicating that the study aimed to recruit an adequate number of participants. Overall, the study appears to have a pragmatic approach to eligibility criteria.

Score: [4]

Recruitment:

1. “T‎he pregnant women were randomly divided into three groups at a university hospital in the suburbs of Sao Paulo, Brazil, in order to receive either acupressure treatment, a placebo or participate as part of a control group.” [Quote 1]

2. “T‎he study used the single-blind method (participants in the SP6 and TG groups did not know what group they were in).” [Quote 2]

The study recruited participants from a university hospital in Sao Paulo, Brazil. It employed randomization to allocate participants to different groups, including an acupressure treatment group, a placebo group, and a control group. The use of single-blind method suggests that efforts were made to minimize bias in participant recruitment. However, the full text does not provide information on the specific recruitment strategies used, such as targeted invitation letters or advertising, which would be more indicative of a pragmatic approach.

Score: [3]

Setting:

1. “W‎e undertook a controlled and randomized clinical test (based on the consort diagram) employing the use of pragmatism. It was carried out between January and August of 2013. The subjects were pregnant women admitted to a teaching tertiary public hospital on the outskirts of the state of Sao Paulo, Brazil.” [Quote 1]

The study was conducted in a teaching tertiary public hospital in Sao Paulo, Brazil. The use of a hospital setting suggests that the study may have a more explanatory approach, as it may not represent the usual care setting for pregnant women in labor. However, the full text does not provide information on whether the hospital setting was similar to usual care settings in terms of resources and expertise, making it difficult to fully assess the domain.

Score: [NA]

Organisation:

1. “T‎he researcher that was responsible for applying the acupressure went through 32 hours’ worth of training.” [Quote 1]

2. “T‎he pregnant women in labor obtained normal obstetrical treatment. Where the study was carried out, the following was permitted: the presence of someone to accompany the pregnant lady, the use of methods other than drugs such as taking a shower, massages in the lower back region and breathing exercises as well as liberty of movement (in cases where this did not go against medical advice).” [Quote 2]

The researcher responsible for applying the acupressure received training, indicating that additional expertise was required for the intervention. The study also mentions that the pregnant women received normal obstetrical treatment, including the presence of a support person and the use of non-drug methods for pain relief. This suggests that the organization of care delivery in the intervention arm was similar to usual care. However, the full text does not provide information on whether additional resources or staff levels were required for the intervention, making it difficult to fully assess the domain.

Score: [NA]

Flexibility (delivery):

1. “T‎he SP6 group with the pregnant women in labor received deep pressure (± 5kg) with fast decompression applied to their thumbs which did not bring about any discomfort.” [Quote 1]

The acupressure intervention in the study involved applying deep pressure to the SP6 point on the thumbs of the pregnant women in labor. The description suggests that there was a specific protocol for delivering the intervention, indicating a more explanatory approach with strict guidelines for delivery.

Score: [2]

Flexibility (adherence):

1. “T‎he pregnant women in labor where encouraged during the CB to breath in and out deeply in the direction of the thorax during the contractions and the intervals in orde for their bodies to be totally relaxed (slow thorax-abdomen breathing rhythm).” [Quote 1]

The full text does not provide information on any specific requirements or measures to improve adherence to the intervention. However, it mentions that the pregnant women were encouraged to practice deep breathing during contractions and intervals. This suggests that there may not have been strict requirements for adherence to the intervention, indicating a more pragmatic approach.

Score: [4]

Follow-up:

1. “V‎AS was used to evaluate the pain and for pre-developed questions. The women were able to classify their perception of the pain.” [Quote 1]

The study used the Visual Analogue Scale (VAS) to measure pain and collected data at multiple time points, including before the treatment, 20 minutes after the treatment, and 60 minutes after the treatment. The use of multiple time points for data collection suggests a more explanatory approach with more intensive measurement and follow-up compared to usual care.

Score: [2]

Primary outcome:

1. “T‎he results show that the use of acupressure on the SP6 point is a complementary method that is non-invasive and can alleviate pain during childbirth, without presenting any adverse effects for pregnant women in labor and neonate women.” [Quote 1]

The primary outcome of the study was the alleviation of pain during childbirth through the use of acupressure on the SP6 point. The outcome is directly relevant to the participants and addresses a key concern in usual care. The study provides evidence that the intervention can achieve the desired outcome, suggesting a more pragmatic approach.

Score: [5]

Primary analysis:

1. “T‎here were statistical differences (p<0.0001, Fridman test) in the VAS values for each group for the three times when the evaluations were done.” [Quote 1]

The full text does not provide detailed information on the primary analysis of the data, such as whether intention-to-treat analysis was used or if all available data were included. However, it mentions that there were statistical differences in the VAS values for each group at multiple time points. Without further information, it is difficult to fully assess the domain.

Score: [NA]

Effectiveness of a partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease: a pragmatic randomized controlled trial (2015), PragQoL

Eligibility:

1. “E‎xcluded were individuals who had another major disease (among them individuals with asthma who had more than 200 ml or 12% increase in FEV1 after inhalation of 200 μg albuterol in the post-bronchodilator spirometry), who were non-Icelandic speaking, not capable of travelling to the treatment site and those who had participated in a structured rehabilitation programme for people with COPD 6 months prior to the screening.” [Score: 4]

Recruitment:

1. “A‎ll potentially relevant patients (n = 291) were contacted for enrolment in the study from primary healthcare settings (n = 8) and the offices of private lung physicians (n = 6) in the Reykjavik capital area of Iceland.” [Score: 4]

2. “T‎here were 119 patients who started participation, with 100 completing the study.” [Score: 4]

Setting:

1. “T‎he treatment site was a clinical research centre located on a university-hospital campus.” [Score: 3]

Organisation:

1. “T‎he intervention was an addition to traditional health care which the control group received. Traditional health care refers to services provided by general practitioners at primary health care centres and visits to lung physicians based on referral from general practitioners or self-initiated appointments.” [Score: 4]

Flexibility (delivery):

1. “T‎he theoretical framework, Partnership with people with COPD and their families, was the basis for this intervention. It was adjusted to the particular needs of young people with COPD in its early stages.” [Score: 4]

Flexibility (adherence):

1. “O‎f those, 58% (14/24) participated in the smoking cessation treatment.” [Score: 4]

Follow-up:

1. “D‎ata were collected at baseline and at month 12. Additionally, data collection was carried out in the experimental group at month 6 after the last treatment session.” [Score: 4]

Primary outcome:

1. “T‎he 6-month partnership-based self-management programme had benefits on the perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles, activities and interests for young patients with the disease in its early stages.” [Score: 4]

Primary analysis:

1. “I‎ntention-to-treat analysis was not carried out.” [Score: 2]

Accessibility, acceptability, and effectiveness in primary care of routine telephone review of asthma: pragmatic, randomised controlled trial (2003), PragQoL

Eligibility:

1. “F‎rom their computerised asthma registers the practices identified adults (⩾18 years) who had asked for a bronchodilator inhaler prescription in the previous six months but who had not had a routine asthma review in the preceding 11 months.” [1]

2. “P‎atients were excluded if the diagnosis of asthma had been made within the previous year, if they had chronic obstructive pulmonary disease, if communication difficulties made a telephone consultation impossible, or (at the general practitioner’s request) for major social or medical reasons.” [1]

3. “O‎ur participants were slightly older than the total eligible population and may not be wholly representative of all adults with asthma in these practices.” [2]

Score: [4]

Recruitment:

1. “P‎atients were sent a letter from their practice informing them that they had been allocated to receive a telephone review and that they should expect a call from the asthma nurse within a month.” [1]

2. “N‎urses were told to make up to four attempts to contact the patient by phone.” [1]

3. “T‎elephone consultations are safe alternatives in the triage of requests for same day appointments and out of hours care.” [2]

Score: [4]

Setting:

1. “F‎our general practices in England.” [1]

2. “O‎ur practices were all “asthma interested”—they all had specialist nurses with considerable experience of providing asthma care, potentially enhancing their skills to undertake telephone consultations.” [2]

Score: [3]

Organisation:

1. “O‎ur study aimed to reflect, as far as possible, normal care of patients with asthma in the participating practices. We asked nurses not to change their clinical practice.” [2]

Score: [5]

Flexibility (delivery):

1. “N‎urses were given no instructions about the content of the review except that it should reflect their normal practice and be appropriate to each patient’s clinical need.” [1]

Score: [5]

Flexibility (adherence):

Score: [NA]

Follow-up:

1. “F‎ollow up questionnaires on morbidity and satisfaction with the consultation were sent to the patients at three months.” [1]

Score: [5]

Primary outcome:

1. “P‎rimary outcome measures were the proportion of patients reviewed within three months of randomisation and change in asthma related quality of life, as measured by the Juniper mini asthma quality of life questionnaire.” [1]

Score: [5]

Primary analysis:

1. “O‎n an intention to treat analysis, 101 of the 137 patients (74%) allocated to the telephone arm were reviewed, compared with 68 of the 141 patients (48%) in the face to face consultation arm.” [1]

Score: [5]

The outcome and cost-effectiveness of nurse-led care in people with rheumatoid arthritis: a multicentre randomised controlled trial (2014), PragQoL

Eligibility:

1. “T‎he inclusion criteria were: a positive diagnosis of RA (1987 American College of Rheumatology (ACR) criteria),29 age 18 years or older and the ability to complete questionnaires unaided. Exclusions were: unstabilised concomitant disease, awaiting surgery and already receiving care from the practitioners involved in the study.” [Score: 4]

Recruitment:

1. “T‎he study was conducted in outpatient clinics of 10 rheumatology centres across the UK.” [Score: 4]

Setting:

1. “T‎he study was conducted in outpatient clinics of 10 rheumatology centres across the UK.” [Score: 4]

Organisation:

1. “T‎his study required three practitioners at each centre; a CNS, a rheumatologist and a blind independent assessor. Nine CNS and 10 rheumatologists delivered the interventions. The CNS had a median experience of 10 years in their current post while the rheumatologists had a median of 9 years at consultant level.” [Score: 4]

Flexibility (delivery):

1. “T‎he NLC interventions usually include allocated 30-min time slots in which the CNS takes history, performs physical examination, pain control, prescribing or recommending medication and dosage changes, intra-articular or intramuscular steroid injections, provision of patient education, psychosocial support and ordering blood tests or X-rays.” [Score: 4]

Flexibility (adherence):

1. “N‎LC has lower consultation costs.” [Score: 4]

Follow-up:

1. “P‎atients were seen by their respective practitioners at baseline and at weeks 13, 26, 39 and 52.” [Score: 4]

Primary outcome:

1. “T‎he primary outcome was the disease activity score (DAS28) assessed at baseline, weeks 13, 26, 39 and 52; the non-inferiority margin being DAS28 change of 0.6.” [Score: 4]

Primary analysis:

1. “A‎nalysis followed per-protocol (PP) and intention-to-treat (ITT) approaches.” [Score: 4]

A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk (2015), PragQoL

Eligibility:

1. “M‎en and women aged ≥18 years at high CVD risk, defined as either established CVD (history of coronary, ischaemic cerebrovascular, or peripheral vascular disease) or an estimated five-year CVD risk of ≥15% (using the Framingham risk equation, including a 5% increment for Aboriginal or Torres Strait Islander identification)21 were eligible.” [Score: 5]

Recruitment:

2. “P‎articipants were excluded if it was felt clinically inappropriate to alter medications.” [Score: 5]

Setting:

3. “A‎ll participants were treated by their regular doctor following randomization.” [Score: 5]

Organisation:

4. “T‎he Kanyini GAP trial was designed to be highly pragmatic with the prescribing, dispensing and payment for polypill occurring identically to what would be usual care, if the polypill were to be marketed in Australia and subsidized through the Pharmaceutical Benefits Scheme.” [Score: 5]

Flexibility (delivery):

5. “N‎o attempt was made to influence any other aspect of their management. The doctor could, at any time, change prescription to the alternative polypill version, add drugs on top of the polypill, or withdraw the polypill and substitute individual drugs of their choice.” [Score: 5]

Flexibility (adherence):

6. “T‎he adherence outcome was a composite of adherence to all three treatment modalities, but there were smaller adherence improvements for each individual treatment modality.” [Score: 4]

Follow-up:

7. “P‎articipants attended the primary healthcare centres for trial assessments at randomization and 12 month intervals thereafter.” [Score: 5]

Primary outcome:

8. “P‎rimary outcomes were self-reported use of indicated combination treatment (antiplatelet, statin and ≥2 BP lowering therapies for ≥4 of the previous seven days) at study end; and changes in systolic BP and total cholesterol from baseline to study end.” [Score: 5]

Primary analysis:

9. “A‎ll analyses were conducted on an intention-to-treat basis without imputation of missing data.” [Score: 5]

Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial (2015), PragQoL

Eligibility:

1. “P‎atients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.” - This quote indicates that the trial followed patients for a relatively long period of time, which suggests that the eligibility criteria were pragmatic and allowed for inclusion of patients who would typically be followed up in usual care. [Score: 4]

Recruitment:

1. “T‎he PROFHER collaborators recruited patients for this pragmatic, open, multicenter, parallel-group, superiority, randomized clinical trial between September 2008 and April 2011 from orthopedic departments (fracture clinics or wards) at 32 acute UK National Health Service hospitals.” - This quote suggests that the trial recruited patients from usual care settings, such as orthopedic departments in hospitals, which indicates a pragmatic approach to recruitment. [Score: 4]

Setting:

1. “T‎he PROFHER collaborators recruited patients for this pragmatic, open, multicenter, parallel-group, superiority, randomized clinical trial between September 2008 and April 2011 from orthopedic departments (fracture clinics or wards) at 32 acute UK National Health Service hospitals.” - This quote indicates that the trial was conducted in multiple centers, including acute UK National Health Service hospitals, which suggests a pragmatic approach to the setting. [Score: 4]

Organisation:

1. “I‎t was emphasized that good standards of care, both surgical and nonsurgical, should be provided throughout the treatment pathway for the injury, including surgical care or management of the sling, postoperative care, and rehabilitation in both groups.” - This quote suggests that the trial aimed to provide care that is consistent with usual care standards, indicating a pragmatic approach to organization. [Score: 4]

Flexibility (delivery):

1. “I‎t was emphasized that good standards of care, both surgical and nonsurgical, should be provided throughout the treatment pathway for the injury, including surgical care or management of the sling, postoperative care, and rehabilitation in both groups.” - This quote suggests that the trial aimed to provide care that is consistent with usual care standards, indicating a pragmatic approach to the delivery of the intervention. [Score: 4]

Flexibility (adherence):

1. “P‎articipating hospitals did not introduce new or experimental interventions for these fractures during the study.” - This quote suggests that there were no specific measures to improve adherence to the intervention, indicating a more explanatory approach. However, since this domain is not applicable to surgical trials, the score should be left blank. [Score: NA]

Follow-up:

1. “P‎atients were followed up for 2 years (up to April 2013) and 215 had complete follow-up data.” - This quote indicates that the trial followed patients for a relatively long period of time, which suggests that the follow-up was pragmatic and similar to what would be done in usual care. [Score: 4]

Primary outcome:

1. “T‎he primary outcome was the Oxford Shoulder Score (range, 0-48; higher scores indicate better outcomes) assessed during a 2-year period, with assessment and data collection at 6, 12, and 24 months.” - This quote indicates that the primary outcome was patient-reported and relevant to participants, as it assessed their shoulder function and pain. [Score: 5]

Primary analysis:

1. “A‎nalyses followed a prespecified analysis plan, endorsed by the data monitoring and ethics committee, and were performed using Stata version 12 (StataCorp). All analyses were on an intention-to-treat basis and included all randomized patients in the groups to which they were randomized.” - This quote suggests that the primary analysis included all randomized patients and followed an intention-to-treat approach, indicating a pragmatic approach to the analysis. [Score: 4]

Promoting physical activity in older people in general practice: ProAct65+ cluster randomised controlled trial (2015), PragQoL

Eligibility:

1. “P‎atients were eligible to participate if they were: community dwelling aged ≥65 years; independently mobile (with or without a walking aid); and physically able to take part in group exercise.” [1]

2. “P‎atients were excluded if they: had experienced ≥3 falls in the previous year; had unstable clinical conditions; would be unable to follow instructions about exercise safely; or were receiving palliative care.” [1]

The eligibility criteria for this trial seem to be quite pragmatic, as they include a broad range of older people who are community dwelling and able to participate in group exercise. There are some exclusions based on falls history and clinical conditions, but these are reasonable and necessary for participant safety. Score: [4]

Recruitment:

1. “P‎ractices were recruited with assistance from Primary Care Research Networks for London, Derby, and Nottingham. Patients aged ≥65 years were identified by searches of computerised medical records and invited to participate by letter from their GP.” [1]

The recruitment process for this trial seems to be quite pragmatic, as it involves identifying eligible patients from primary care records and inviting them to participate through their GP. This is a common and feasible approach that would be used in usual care. Score: [5]

Setting:

1. “P‎ragmatic three-arm, parallel-design cluster randomised controlled trial involving 1256 people aged ≥65 years (of 20 507 invited) recruited from 43 general practices in London, Nottingham, and Derby.” [1]

The trial was conducted in general practices in London, Nottingham, and Derby, which are typical settings for primary care. This suggests a pragmatic approach to the setting, as it involves multiple sites that are representative of usual care. Score: [5]

Organisation:

1. “T‎he interventions were the home-based Otago Exercise Programme (OEP), and a group-based exercise programme called Falls Management Exercise (FaME).” [1]

2. “V‎olunteer peer mentors supported participants in the OEP arm, and weekly FaME classes were run in local venues by postural stability instructors trained to work with older people.” [1]

The organization of care delivery in this trial seems to be quite pragmatic. The interventions were designed to be feasible and deliverable in a primary care setting, with the OEP being home-based and the FaME classes being run in local venues. The use of volunteer peer mentors and postural stability instructors also suggests a pragmatic approach to utilizing available resources. Score: [4]

Flexibility (delivery):

1. “T‎he interventions were the home-based Otago Exercise Programme (OEP), and a group-based exercise programme called Falls Management Exercise (FaME).” [1]

2. “T‎he programmes included the following progression: OEP — ankle weights and hand holds; and FaME — resistance bands and hand holds, plus a move to more dynamic balance work and floor work with postural stability instructors.” [1]

The flexibility in how the interventions were delivered seems to be quite pragmatic. The OEP and FaME programs included different exercises and progressions, allowing for individual tailoring and adaptation based on participant needs and capabilities. Score: [4]

Flexibility (adherence):

1. “A‎dherence was defined as (minutes spent exercising/intended minutes) 100%, where patients with values exceeding 75% were regarded as ‘adherent’.” [1]

The trial did not explicitly mention any measures or interventions to improve adherence, but it did define adherence as a percentage of intended minutes spent exercising. This suggests a pragmatic approach to adherence, as it allows for some flexibility and recognizes that participants may not always meet the intended minutes. Score: [3]

Follow-up:

1. “P‎articipants were followed up every 6 months after the end of the intervention period, until 24 months.” [1]

The follow-up schedule for this trial seems to be quite pragmatic, as it involves regular follow-up visits every 6 months for up to 24 months. This is a reasonable and feasible approach that would be used in usual care. Score: [4]

Primary outcome:

1. “T‎he primary outcome was the proportion of participants who reported reaching ≥150 minutes of MVPA per week.” [1]

The primary outcome of this trial seems to be quite pragmatic, as it focuses on a relevant and meaningful outcome for participants - reaching the recommended physical activity target. This is a patient-centered outcome that is of obvious importance to participants. Score: [5]

Primary analysis:

1. “P‎articipants were analysed in the groups to which they were randomised, regardless of whether they received the intervention or not, and multiple imputation was used to include all participants in the analyses.” [1]

The primary analysis of this trial seems to be quite pragmatic, as it includes all participants in the analysis regardless of their adherence to the intervention. This intention-to-treat approach is commonly used in pragmatic trials and allows for a more realistic assessment of the intervention’s effectiveness. Score: [5]

MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial (2010), PragMS

Eligibility:

• “A‎ total of 164 patients with MS referred themselves after having received information via the outpatient neurology clinic of the University Hospital Basel, other physicians, or advertisements posted in the Swiss Multiple Sclerosis Society Bulletin.” [1]

• “N‎eurologists verified all patients for the following inclusion criteria: 1) diagnosis of relapsing-remitting (but no more than 2 exacerbations within the last year) or secondary progressive MS21 and 2) an Expanded Disability Status Scale (EDSS)22 score of ≤6 (no to moderately severe disability), with ≤1 step increase within the last year.” [1]

• “E‎xcluded were patients with reported or medically recorded diagnoses of current serious psychological disorders other than depression and anxiety syndromes, evidence of dementia as indicated by testing below the fifth percentile in at least 3 of 6 dimensions of neuropsychological functioning (i.e., attention and concentration, processing speed, executive function, verbal memory, and verbal processing), other currently life-threatening or severely disabling physical disorders, current MS exacerbation, symptomatic MS medication altered in the last 3 months, other disorders of the CNS, pregnancy, or inability to speak or read German.” [1]

The eligibility criteria for this trial appear to be relatively pragmatic. Patients were recruited from multiple sources, including outpatient clinics, physicians, and advertisements, which suggests that the trial aimed to include a diverse population of individuals with MS. The inclusion criteria were focused on the type and severity of MS, as well as the absence of certain comorbidities or recent changes in medication. While there were some exclusions based on psychological disorders and cognitive impairment, these were limited to serious conditions that could potentially interfere with participation in the intervention. Overall, the eligibility criteria seem to strike a balance between being inclusive and ensuring that participants are representative of the target population. Score: [4]

Recruitment:

• “A‎ total of 164 patients with MS referred themselves after having received information via the outpatient neurology clinic of the University Hospital Basel, other physicians, or advertisements posted in the Swiss Multiple Sclerosis Society Bulletin.” [1]

The recruitment methods used in this trial appear to be relatively pragmatic. Patients were recruited through multiple channels, including outpatient clinics, physicians, and advertisements in a MS society bulletin. This suggests that efforts were made to engage with a diverse population of individuals with MS and that the recruitment methods were similar to those used in usual care settings. However, the full text does not provide detailed information about the specific strategies used to recruit participants, such as targeted invitation letters or advertising in newspapers or radio. Therefore, it is difficult to fully assess the extent of extra effort made to recruit participants. Score: [3]

Setting:

• “A‎ total of 164 patients with MS referred themselves after having received information via the outpatient neurology clinic of the University Hospital Basel, other physicians, or advertisements posted in the Swiss Multiple Sclerosis Society Bulletin.” [1]

The setting of this trial appears to be relatively pragmatic. Patients were recruited from multiple sources, including outpatient clinics and physicians, which suggests that the trial was conducted in settings that are similar to usual care. However, the full text does not provide information about the specific locations where the intervention and usual care were delivered. Therefore, it is difficult to fully assess the extent to which the trial setting differed from usual care settings. Score: [3]

Organisation:

• “A‎ll patients in the usual care (UC) group (and in the MBI group) received regular, currently optimal medical care during the duration of the study, as provided by the neurology department of the hospital. This included one medical examination at preintervention and another at 6 months postintervention, with additional measures as individually required.” [1]

The organization of care delivery in this trial appears to be relatively pragmatic. The usual care group received regular medical care provided by the neurology department of the hospital, which suggests that the trial used existing resources and infrastructure for delivering care. The additional measures provided as individually required also indicate a flexible approach to care delivery. However, the full text does not provide detailed information about any additional resources, staff levels, or training provided specifically for the intervention arm of the trial. Therefore, it is difficult to fully assess the extent to which the organization of care delivery differed between the intervention and usual care groups. Score: [4]

Flexibility (delivery):

• “M‎BI closely followed the program of mindfulness-based stress reduction23 and included 1) a personal intake interview to define realistic goals of participants and establish personal rapport; 2) 8 weekly 2.5-hour classes in mindfulness practices (10–15 participants/group; exercises did not exceed patients’ level of functioning); 3) one Saturday, 7-hour session at week 6; 4) homework assignments (approximately 40 minutes/day), emphasized as essential to success of the program; 5) a postintervention interview to evaluate personal experiences, goal attainment, and future maintenance of acquired skills.” [1]

The flexibility in how the intervention was delivered appears to be relatively pragmatic. The intervention consisted of a structured 8-week program with a combination of group sessions, individual interviews, and homework assignments. The program was tailored to the participants’ goals and abilities, and the exercises did not exceed their level of functioning. The inclusion of a postintervention interview to evaluate personal experiences and goal attainment suggests a focus on individualized care. However, the full text does not provide information about the extent to which participants were allowed to deviate from the program or make adjustments based on their individual needs. Therefore, it is difficult to fully assess the flexibility in how the intervention was delivered. Score: [4]

Flexibility (adherence):

• This domain is not applicable to this trial as there is no compliance issue after consent has been given. Score: [NA]

Follow-up:

• “A‎ssessments were made at baseline, postintervention, and 6 months follow-up.” [1]

The intensity of measurement and follow-up in this trial appears to be relatively pragmatic. Assessments were conducted at baseline, postintervention, and 6 months follow-up, which is a reasonable follow-up period for evaluating the effects of the intervention. However, the full text does not provide detailed information about the specific measurements and follow-up procedures used in the trial, such as the frequency and duration of the assessments. Therefore, it is difficult to fully assess the extent to which the intensity of measurement and follow-up differed from usual care. Score: [3]

Primary outcome:

• “P‎rimary outcomes included disease-specific and disease-aspecific HRQOL, depression, and fatigue.” [1]

The relevance of the trial’s primary outcome to participants appears to be relatively pragmatic. The primary outcomes included measures of health-related quality of life (HRQOL), depression, and fatigue, which are all outcomes that are likely to be important to individuals with multiple sclerosis (MS). The full text does not provide information about the specific measures used to assess these outcomes, but the inclusion of disease-specific and disease-aspecific HRQOL measures suggests a focus on outcomes that are directly relevant to the participants’ experience of living with MS. Score: [5]

Primary analysis:

• “E‎mploying intention-to-treat analysis, MBI, compared with UC, improved nonphysical dimensions of primary outcomes at postintervention and follow-up (p < 0.002); effect sizes, 0.4–0.9 posttreatment and 0.3–0.5 at follow-up.” [1]

The extent to which all data were included in the analysis of the primary outcome is not explicitly stated in the full text. However, the use of intention-to-treat analysis suggests that all randomized participants were included in the analysis, regardless of their adherence to the intervention or completion of follow-up assessments. Therefore, it can be inferred that all available data were included in the analysis of the primary outcome. Score: [4]

Effect of an intensive 3-day social cognitive treatment (can do treatment) on control self-efficacy in patients with relapsing remitting multiple sclerosis and low disability: A single-centre randomized controlled trial (2019), PragMS

Eligibility:

1. “I‎n a 6-month, single-centre, randomized (1:1), unmasked, controlled trial in RRMS patients with Expanded Disability Status Scale (EDSS) score ≤4.0…” - This quote indicates that the trial included RRMS patients with a specific disability score. [Score: 3]

Recruitment:

1. “P‎articipants were recruited from all over the Netherlands by the patient organisation NMSF, Rotterdam, the Netherlands.” - This quote suggests that participants were recruited through a patient organization, which may have involved targeted invitation letters and advertising. [Score: 2]

Setting:

1. “A‎ total of 158 patients were screened for eligibility…The enrolment started February 2013 and ended April 2016.” - This quote indicates that the trial was conducted over a period of several years and involved multiple sites. [Score: 2]

Organization:

1. “T‎he multidisciplinary team included a psychiatrist, psychiatric nurse, neurologist, registered nurse specialized in MS, physiotherapist, dance therapist, and a person with MS.” - This quote suggests that the trial involved a multidisciplinary team with specialized expertise. [Score: 3]

Flexibility (delivery):

1. “C‎DT’s components are large group sessions, small group sessions, consultations (carrousel), a theatre evening, and start of the day with a joint activity (optional).” - This quote indicates that the intervention involved multiple components and allowed for some flexibility in delivery. [Score: 4]

Flexibility (adherence):

1. “N‎o safety concerns or adverse events were noted during the intervention.” - This quote suggests that adherence to the intervention was not a major issue. [Score: 5]

Follow-up:

1. “F‎ollow-up assessments were at one, three and six months.” - This quote indicates that participants were followed up at multiple time points over a period of six months. [Score: 4]

Primary outcome:

1. “T‎he primary study outcome was the change in control self-efficacy, assessed by the Multiple Sclerosis Self-Efficacy Scale (MSSES), at six months.” - This quote indicates that the primary outcome was directly relevant to the participants. [Score: 5]

Primary analysis:

1. “A‎ll endpoints were analyzed according to the intention-to-treat principle using an ANCOVA with the 6-month value as dependent variable, and condition, baseline value, disease duration and gender as independent variables.” - This quote suggests that the primary analysis included all available data and followed an intention-to-treat approach. [Score: 5]

The clinical- and cost-effectiveness of functional electrical stimulation and ankle-foot orthoses for foot drop in Multiple Sclerosis: a multicentre randomized trial (2019), PragMS

Eligibility:

1. “P‎articipants required to have a clinical diagnosis of Multiple Sclerosis, persistent foot drop (lasting a minimum of three months) observed during a 5-minute walk test, stable disease (no change in the Extended Disability Status Score12 or relapse in previous three months), 5° of passive dorsiflexion and tolerance of functional electrical stimulation. Participants were excluded if they had previously used functional electrical stimulation or an ankle-foot orthosis for foot drop, moderate to severe cognitive impairment (scored < 26, Montreal Cognitive Assessment),13 foot drop due to other disorders, other conditions significantly affecting gait, contraindications to functional electrical stimulation, marked proximal weakness, plantar flexor spasticity, stance phase instability or severe lower limb/trunk ataxia affecting gait.” [NA]

2. “E‎ighty-five participants met the criteria for inclusion and consented to participate in the study between September 2014 and January 2017.” [NA]

Recruitment:

1. “P‎otential participants known to Multiple Sclerosis healthcare practitioners working across seven outpatient centres in Scotland – Ayrshire & Arran, Greater Glasgow & Clyde, Dumfries and Galloway, Lanarkshire, Lothian, Fife and Tayside – were informed of the study and issued with a participant information sheet. Potential participants contacted the researchers if they were interested in participating.” [NA]

Setting:

1. “S‎even Multiple Sclerosis outpatient centres across Scotland.” [Score: 5]

Organisation:

1. “P‎articipants randomized to the usual care group were fitted with a custom-made, solid, ankle-foot orthosis by an orthotist, within four weeks of their initial assessment.” [Score: 5]

Flexibility (delivery):

1. “P‎articipants in both groups were instructed to gradually increase the wear of their devices over the first six weeks.” [Score: 5]

Flexibility (adherence):

1. “N‎o information provided.” [NA]

Follow-up:

1. “A‎ssessed at 0, 3, 6 and 12 months.” [Score: 5]

Primary outcome:

1. “W‎alking speed as measured by the 5-minute self-selected walk test.” [Score: 5]

Primary analysis:

1. “A‎ Restricted Maximum Likelihood approach to fitting mixed models was employed to allow intention to treat assumptions to cope with missing data.” [Score: 5]

Overall score: [NA]

Influence of sports climbing and yoga on spasticity, cognitive function, mood and fatigue in patients with multiple sclerosis (2010), PragMS

Eligibility:

1. “2‎0 subjects with relapsing–remitting or progressive MS, 26–50 years of age, with EDSS ≤ 6 and EDSS pyramidal functions score (EDSSpyr) > 2 were enrolled in a randomized prospective study.” [Score: 4] The eligibility criteria for this trial are relatively pragmatic, as they include a broad range of MS patients with different disease types and severity. However, the exclusion of patients with EDSS pyramidal functions score (EDSSpyr) ≤ 2 may limit the generalizability of the results to patients with less severe disease.

Recruitment:

1. “T‎he participants were randomly divided into SC and yoga group.” [Score: 4] The randomization process used in this trial suggests a pragmatic approach to recruitment. However, the full text does not provide information on how participants were recruited or whether any additional efforts were made to engage with patients beyond usual care.

Setting:

1. “S‎C took place in the Training, Occupation and Care Centre under the supervision of two SC instructors with a Slovenian Sports Climbing Committee License.” [Score: 3] The trial was conducted in a specialized setting, the Training, Occupation and Care Centre, which may limit the generalizability of the results to usual care settings. However, the use of licensed SC instructors suggests some level of standardization and expertise in the delivery of the intervention.

Organisation:

1. “T‎he climbing wall with an inclination of 90° and the height of 5 m was adjusted for patients with physical disabilities by adding numerous and bigger holds.” [Score: 4] The trial made adjustments to the climbing wall to accommodate patients with physical disabilities, which suggests a pragmatic approach to the organization of care delivery. However, the full text does not provide information on whether any additional resources or training were provided to the staff involved in delivering the intervention.

Flexibility (delivery):

1. “A‎ll patients were belayed with the “top rope” system, which provided a safe climbing opportunity with the possibility to rest in the wall at any point.” [Score: 4] The use of the ”top rope” system and the ability for patients to rest during climbing suggest a pragmatic approach to the flexibility in how the intervention is delivered. However, the full text does not provide information on whether there were any restrictions or guidelines on how the intervention should be delivered beyond the use of the ”top rope” system.

Flexibility (adherence):

1. “T‎here were no significant improvements in spasticity after SC and yoga.” [Score: NA] This domain is not applicable to this trial as there is no compliance issue after consent has been given.

Follow-up:

1. “B‎oth programs were held once a week for 10 weeks.” [Score: 4] The duration and frequency of the intervention suggest a pragmatic approach to the intensity of measurement and follow-up. However, the full text does not provide information on whether there were any additional measurements or follow-up visits beyond the assessment before and after the programs.

Primary outcome:

1. “T‎here were no significant improvements in spasticity after SC and yoga.” [Score: 4] The primary outcome of spasticity is relevant to participants as it is a common symptom in MS. However, the lack of significant improvements suggests that the trial may have used a more explanatory approach in measuring the primary outcome.

Primary analysis:

1. “D‎ata were analyzed by SPSS program for Windows®, version 17.0. Wilcoxon signed ranks test was used to compare the difference before and after each program.” [Score: 4] The use of intention-to-treat analysis and the inclusion of all available data in the analysis suggest a pragmatic approach to the primary analysis. However, the full text does not provide information on whether any additional analyses were conducted, such as per-protocol or subgroup analyses.

Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation (2016), PragMS

Eligibility:

1. “F‎ifty relapsing patients with multiple sclerosis (MS) who had been on natalizumab therapy ≥24 months and were contemplating natalizumab discontinuation were enrolled.” [Explanatory]

2. “I‎nclusion criteria consisted of: a diagnosis of relapsing MS according to McDonald criteria,19 being on natalizumab therapy for 24 months or longer, aged between 18 and 65 years and an EDSS score of ≤7.0.” [Explanatory]

3. “C‎andidates were excluded from the study if active disease was identified at baseline per clinical (presence of a relapse during the previous 30 days) and/or MRI evaluation (active gadolinium (Gd)-enhancing lesions).” [Explanatory]

Score: [2]

Recruitment:

1. “N‎o information provided in the full text.” [NA]

Score: [NA]

Setting:

1. “T‎his was a prospective, phase IV, 12-month, open-label, single center single-blinded (MRI) randomised study.” [Explanatory]

Score: [2]

Organisation:

1. “N‎o information provided in the full text.” [NA]

Score: [NA]

Flexibility (delivery):

1. “P‎atients in both groups may have received additional optional treatment with intravenous myethylprednisolone (IVMP) in the first 6 months post-natalizumab discontinuation.” [Pragmatic]

Score: [4]

Flexibility (adherence):

1. “N‎o information provided in the full text.” [NA]

Score: [NA]

Follow-up:

1. “A‎ physical examination and neurological assessment was administered at baseline, 3, 6 and 12 months postdiscontinuation (counted from the last natalizumab infusion), as well as during unscheduled visits due to relapses (within 3–5 days of any new symptom development).” [Pragmatic]

Score: [4]

Primary outcome:

1. “T‎o compare two modes of natalizumab cessation interventions: immediate versus tapered down, as measured by serial MRI and the occurrence of relapses during a 12-month period.” [Explanatory]

Score: [2]

Primary analysis:

1. “N‎o information provided in the full text.” [NA]

Score: [NA]

Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients (2016), PragMS

Eligibility:

1. “C‎omparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS.” [1]

2. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

3. “I‎n total, 202 and 426 CARE-MS II patients were randomized to SC IFN-β-1a 44 μg and alemtuzumab 12 mg, respectively.” [3]

Score: [4]

Recruitment:

1. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

Score: [4]

Setting:

1. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

Score: [4]

Organisation:

1. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

Score: [4]

Flexibility (delivery):

1. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

Score: [4]

Flexibility (adherence):

1. “I‎n patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.” [4]

Score: [5]

Follow-up:

1. “M‎ethods have been published elsewhere.12 CARE-MS II was a 2-year, randomized, rater-blinded, active comparator-controlled, head-to-head, trial of alemtuzumab (Lemtrada; Sanofi Genzyme, Cambridge, MA; 12 mg/day on 5 consecutive days at month 0 and on 3 consecutive days at month 12) vs SC IFN-β-1a (Rebif; EMD Serono, Rockland, MA; 44 μg 3 times weekly) in patients with RRMS with inadequate response to prior DMTs (≥1 relapse during IFN-β or glatiramer acetate [GA] treatment [received for ≥6 months]).” [2]

Score: [4]

Primary outcome:

1. “A‎lemtuzumab-treated patients were more likely than SC IFN-β-1a–treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems.” [5]

Score: [5]

Primary analysis:

1. “A‎lemtuzumab-treated patients were more likely than SC IFN-β-1a–treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems.” [5]

Score: [5]

Hockey Fans in Training: A Pilot Pragmatic Randomized Controlled Trial (2017), PragQoL

Eligibility:

1. “M‎ale fans of two ice hockey teams (35–65 yr; body mass index ≥28 kg·m−2) located in Ontario (Canada) were randomized to intervention (Hockey FIT) or comparator (wait-list control).” [1]

2. “E‎ligible participants were male 35–65 yr old with a BMI of ≥28 kg·m−2 and met PA safety requirements (i.e., no risk indicated by the Physical Activity Readiness Questionnaire [36] or clearance from a health care provider).” [2]

3. “O‎ur results are provocative because we found that men who participated in the Hockey FIT program lost weight, increased their steps per day, and improved other clinical outcomes (e.g., systolic BP), their diet, and perceptions of their own health, to a greater extent compared with the controls.” [3]

The full text provides clear information about the eligibility criteria for the trial. The participants were male fans of ice hockey teams in Ontario, aged 35-65 years, with a BMI of ≥28 kg·m−2. They also had to meet the physical activity safety requirements. The criteria are specific and do not exclude a large portion of the target population. Score: [4]

Recruitment:

1. “R‎ecruitment of 80 eligible participants was completed in a short time frame using methods that were easy to implement and with no added costs.” [4]

2. “A‎cross both sites, the most successful methods of recruitment included communication from the hockey team via e-mail or social media (e.g., Twitter) and word of mouth, where 40% and 36% of men were recruited, respectively.” [4]

3. “A‎lthough this study was designed as a pilot trial, we achieved many statistically and clinically important differences between groups at 12 wk, favoring the Hockey FIT group.” [4]

The full text provides information about the recruitment methods used, including communication from the hockey team via e-mail or social media, word of mouth, traditional media sources, posters, and handouts. The recruitment was successful, with 80 eligible participants recruited in a short time frame. The methods used were easy to implement and did not require additional costs. Score: [4]

Setting:

1. “W‎e conducted a pilot, pragmatic randomized controlled trial (pRCT; parallel groups, stratified by site) in Ontario, Canada.” [2]

2. “W‎e used a pragmatic approach for the program venue at each site, using a combination of the hockey team’s arena and an affiliated health club facility.” [2]

3. “I‎n this study, we sought to reflect real-world conditions, in preparation for the definitive trial, where our goal will be to determine the effect of this program under conditions we expect it to be applied after research.” [4]

The full text provides information about the setting of the trial, which took place in Ontario, Canada. The program venue was a combination of the hockey team’s arena and an affiliated health club facility, reflecting real-world conditions. The setting of the trial is similar to the usual care setting, with the program being implemented in locations that are accessible to the target population. Score: [4]

Organisation:

1. “T‎he Hockey FIT program was delivered over 12 weekly, 90-min sessions by Hockey FIT coaches (coach to participant ratio 2:20) from the central research team.” [2]

2. “P‎articipants were encouraged to continue with their lifestyle prescriptions and sustain their behavior changes with the support of free-of-charge eHealth tools: 1) HealtheSteps smartphone app providing tools to track and sustain PA (www.healthesteps.ca) and 2) Hockey FIT social network, a secure Web-based network tailored to each site and including only group members and coaches.” [2]

3. “A‎lthough this study was designed as a pilot trial, we achieved many statistically and clinically important differences between groups at 12 wk, favoring the Hockey FIT group.” [4]

The full text provides information about the organization of care delivery in the intervention arm of the trial. The Hockey FIT program was delivered by Hockey FIT coaches from the central research team. Participants were also provided with free eHealth tools, including a smartphone app and a secure web-based network. The intervention arm of the trial had additional resources and support compared to usual care. Score: [3]

Flexibility (delivery):

1. “T‎he Hockey FIT program was delivered over 12 weekly, 90-min sessions by Hockey FIT coaches (coach to participant ratio 2:20) from the central research team.” [2]

2. “T‎wice throughout the program, participants completed the validated Step Test and Exercise Prescription to receive a personalized target heart rate to strive for during aerobic activities.” [2]

3. “A‎t the start of the program, more time was allocated to classroom education, but as the program progressed, more time was spent on group-based exercise.” [2]

The full text provides information about the flexibility in how the intervention is delivered. The Hockey FIT program consists of 12 weekly sessions, with a combination of classroom-based teaching and group-based exercise. The program also includes personalized exercise prescriptions based on the Step Test. The intervention allows for some flexibility in the delivery of the program, with a focus on individualized exercise goals. Score: [3]

Flexibility (adherence):

1. “P‎articipants were encouraged to continue with their lifestyle prescriptions and sustain their behavior changes with the support of free-of-charge eHealth tools.” [2]

2. “F‎or the remaining 30 men (i.e., program completers), the mean (SD) for percentage of sessions attended was 81.7% (13.7).” [4]

3. “A‎lthough this study was designed as a pilot trial, we achieved many statistically and clinically important differences between groups at 12 wk, favoring the Hockey FIT group.” [4]

The full text does not provide enough information to assess the flexibility in how participants must adhere to the intervention. However, it is mentioned that participants were encouraged to continue with their lifestyle prescriptions and sustain their behavior changes with the support of eHealth tools. The program completers attended a high percentage of sessions, indicating good adherence to the intervention. Score: [NA]

Follow-up:

1. “T‎rial retention was high at 12 wk (in both groups) and 12 months (intervention group only), and only one individual stated that he withdrew due to trial procedures (i.e., randomization).” [4]

2. “B‎etween 12 wk and 12 months (intervention group only), two individuals who had not attended the 12-wk measurement sessions returned to complete the 12-month measurement sessions and an additional five individuals were lost to follow-up.” [4]

3. “F‎urthermore, men were able to maintain most of these outcomes 12 months later, after a minimally supported phase, showing promise for long-term sustainability.” [4]

The full text provides information about the follow-up of participants in the trial. Trial retention was high at both 12 weeks and 12 months, with only a small number of individuals lost to follow-up. The intervention group was able to maintain most of the outcomes at 12 months, indicating good follow-up and long-term sustainability. Score: [4]

Primary outcome:

1. “A‎t 12 wk, the intervention group lost 3.6 kg (95% confidence interval, −5.26 to −1.90 kg) more than the comparator group (P < 0.001) and maintained this weight loss to 12 months.” [2]

2. “T‎he intervention group also demonstrated greater improvements in other clinical measures, physical activity, diet, and self-rated health at 12 wk; most sustained to 12 months.” [2]

3. “O‎ur results are provocative because we found that men who participated in the Hockey FIT program lost weight, increased their steps per day, and improved other clinical outcomes (e.g., systolic BP), their diet, and perceptions of their own health, to a greater extent compared with the controls.” [3]

The full text provides information about the primary outcome of the trial, which is weight loss. The intervention group lost significantly more weight than the comparator group at 12 weeks and maintained this weight loss at 12 months. The intervention group also demonstrated greater improvements in other clinical measures, physical activity, diet, and self-rated health. The primary outcome is relevant to the participants and is measured at a similar time frame to usual care. Score: [5]

Primary analysis:

1. “W‎e analyzed outcome data to examine the potential effectiveness of the Hockey FIT program on the basis of an intent-to-treat approach.” [2]

2. “W‎e ran an additional linear mixed-effects model within the intervention group only to obtain exploratory estimates for mean change from baseline to 12 months.” [2]

3. “W‎e analyzed the data using likelihood-based methods, which are well known to provide unbiased results under the more general assumption of missing at random.” [4]

The full text provides information about the primary analysis of the trial. The outcome data were analyzed using an intent-to-treat approach, which is a pragmatic approach that includes all randomized participants regardless of compliance with the intervention. An additional analysis was conducted within the intervention group to obtain exploratory estimates for mean change from baseline to 12 months. The analysis methods used are appropriate for a pragmatic trial. Score: [5]

A pilot randomized controlled trial of a tailored cognitive behavioural therapy based intervention for depressive symptoms in those newly diagnosed with multiple sclerosis (2016), PragMS

Eligibility:

1. “I‎nclusion criteria were: 1) having a definite diagnosis of MS from a neurologist; 2) being within 5 years of receiving a diagnosis of MS; 3) scoring at least 10 on the Beck Depression Inventory-II (BDI-II) [26]; 4) not currently undertaking other psychological treatment for depressive or anxiety symptoms for the length of participation in the current trial; 5) speak English fluently; 6) no current or lifetime diagnosis of psychosis; 7) no current substance dependency; 8) no gross cognitive impairment; and 9) no changes to medications prior and during involvement in the trial.” [1]

2. “P‎articipants were recruited through neurologists working in a large MS outpatient clinic at the hospital, advertisements on MS related websites and local press releases.” [2]

3. “T‎he study took place at a large teaching and research hospital in Melbourne, Australia.” [2]

The eligibility criteria for this trial appear to be relatively pragmatic. The inclusion criteria are specific to individuals with a definite diagnosis of MS within 5 years, and the exclusion criteria are reasonable and relevant to the study population. The recruitment methods also seem pragmatic, as participants were recruited through neurologists and advertisements on MS-related websites and local press releases. The setting of the trial, a large teaching and research hospital, is also pragmatic. Score: [4]

Recruitment:

1. “P‎articipants were recruited through neurologists working in a large MS outpatient clinic at the hospital, advertisements on MS related websites and local press releases.” [2]

The recruitment methods used in this trial appear to be relatively pragmatic. Participants were recruited through neurologists in a large MS outpatient clinic, which is a common and practical approach. Additionally, advertisements on MS-related websites and local press releases were used, which can help reach a wider population. Score: [4]

Setting:

1. “T‎he study took place at a large teaching and research hospital in Melbourne, Australia.” [2]

The setting of this trial, a large teaching and research hospital, is relatively explanatory. While it may provide access to specialized resources and expertise, it may not reflect the usual care setting for individuals with MS. Score: [2]

Organization:

1. “T‎he tailored CBT intervention lends from Beck’s cognitive theoretical model for the treatment of depression in adults. Participants were given homework to complete for each of the 8 sessions. All sessions (apart from the first session which was 1.5 h) were 1 h in duration and took place in a clinic room at the hospital. A senior clinical psychologist and a provisional clinical psychologist (supervised by the clinical psychologist) provided the intervention.” [2]

The organization of care delivery in the intervention arm of this trial appears to be relatively pragmatic. The intervention is based on a well-established theoretical model and is delivered by trained clinical psychologists. The sessions take place in a clinic room at the hospital, which is a practical and accessible setting. Score: [4]

Flexibility (delivery):

1. “T‎he CBT intervention consisted of 8 individual modules which focused on CBT based principles and strategies. These strategies included progressive muscle relaxation, controlled breathing exercises, pleasant activity scheduling, problem solving skills, cognitive exercises which helped individuals identify, challenge and manage unhelpful thoughts and beliefs.” [2]

The flexibility in how the intervention is delivered in this trial appears to be relatively pragmatic. The intervention consists of 8 individual modules that focus on CBT-based principles and strategies. The specific strategies used, such as progressive muscle relaxation and problem-solving skills, are practical and applicable to usual care. Score: [4]

Flexibility (adherence):

This domain is not applicable to this trial as there is no compliance issue after consent has been given. Score: [NA]

Follow-up:

1. “A‎ll participants completed the pre, post and 20 week follow up questionnaires.” [2]

The intensity of measurement and follow-up in this trial appears to be relatively pragmatic. Participants completed pre, post, and 20-week follow-up questionnaires, which is a reasonable and practical approach. Score: [4]

Primary outcome:

1. “T‎he primary outcome was level of depressive symptoms at post and at 20 weeks follow up which was measured with the Beck Depression Inventory-II (BDI-II).” [2]

The primary outcome of this trial, level of depressive symptoms measured with the BDI-II, appears to be relevant to participants. Depression is a common and important outcome to assess in individuals with MS. Score: [5]

Primary analysis:

1. “R‎esults of ANCOVAs examining group differences on primary and secondary variables at pre, post and 20 week follow up are presented in Table 2.” [2]

The primary analysis of this trial appears to be relatively pragmatic. Group differences on primary and secondary variables were analyzed using ANCOVAs, which is a common and appropriate statistical method. Score: [4]

Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial (2013), PragQoL

Eligibility:

• “P‎regnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision.” [1]

• Score: [4] The eligibility criteria are somewhat pragmatic as they include pregnant women who are undergoing their first or second caesarean section, which is similar to usual care. However, the criteria exclude women who have a clear indication for a particular surgical technique or material, which is more explanatory.

Recruitment:

• “T‎he trial was discussed with all eligible women and their partners and relatives as appropriate. If the woman agreed to participate, she signed a formal consent form or used the method of recording consent permitted in that setting.” [2]

• Score: [5] The recruitment process seems very pragmatic as it involves discussing the trial with eligible women during their care and obtaining informed consent, which is similar to usual care.

Setting:

• “C‎ORONIS was undertaken at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan.” [2]

• Score: [4] The trial was conducted at multiple sites in different countries, which is somewhat pragmatic. However, the trial was not conducted in a wide range of settings and was limited to specific countries, which is more explanatory.

Organisation:

• “A‎ll investigators, surgeons, and participants were unmasked to treatment allocation.” [2]

• Score: [5] The trial was conducted in an unmasked manner, which is similar to usual care.

Flexibility (delivery):

• “A‎ll non-allocated surgical elements and all other aspects of the caesarean section procedure were undertaken at the discretion of the surgeon.” [2]

• Score: [5] The surgeons had discretion in performing the non-allocated surgical elements, which is similar to usual care.

Flexibility (adherence):

• Not applicable. The full text does not provide information on adherence to the intervention.

Follow-up:

• “D‎ata were collected at trial entry, immediately after surgery, at hospital discharge, and at about 6 weeks after delivery.” [2]

• Score: [5] The follow-up schedule includes data collection at multiple time points, including the 6-week follow-up visit, which is similar to usual care.

Primary outcome:

• “T‎here were no statistically significant differences within any of the intervention pairs for the primary outcome.” [2]

• Score: [5] The trial found no statistically significant differences in the primary outcome, suggesting that the trial’s primary outcome is relevant to participants.

Primary analysis:

• “W‎omen were analysed in the groups into which they were allocated.” [2]

• Score: [5] The primary analysis included all women in the groups to which they were allocated, which is similar to an intention-to-treat analysis and is pragmatic.

Overall, the trial seems to have a pragmatic design, with some domains leaning more towards explanatory. The eligibility criteria, recruitment process, flexibility in delivery, and primary analysis are all pragmatic. However, the setting and organisation of the trial are somewhat explanatory. The trial does not provide enough information to assess the flexibility in adherence domain.

System prompt

You are an expert in clinical trial design and are tasked to assess the PRECIS-2 scores of a trial based on the full text of its publication. You have the following briefing:
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# PRECIS-2 Domains
* Eligibility: To what extent are the participants in the trial similar to those who would receive this intervention if it was part of usual care? For example, score 5 for very pragmatic criteria essentially identical to those in usual care; score 1 for a very explanatory approach with lots of exclusions (e.g. those who don’t comply, respond to treatment, or are not at high risk for primary outcome, are children or elderly), or uses many selection tests not used in usual care.
* Recruitment: How much extra effort is made to recruit participants over and above what that would be used in the usual care setting to engage with patients? For example, score 5 for very pragmatic recruitment through usual appointments or clinic; score 1 for a very explanatory approach with targeted invitation letters, advertising in newspapers, radio plus incentives and other routes that would not be used in usual care.
* Setting: How different is the setting of the trial and the usual care setting? For example, score 5 for a very pragmatic choice using identical settings to usual care; score 1, for a very explanatory approach with only a single centre, or only specialised trial or academic centres.
* Organisation: How different are the resources, provider expertise and the organisation of care delivery in the intervention arm of the trial and those available in usual care? For example, score 5 for a very pragmatic choice that uses identical organisation to usual care; score 1 for a very explanatory approach if the trial increases staff levels, gives additional training, require more than usual experience or certification and increase resources.
* Flexibility (delivery): How different is the flexibility in how the intervention is delivered and the flexibility likely in usual care? For example, score 5 for a very pragmatic choice with identical flexibility to usual care; score 1 for a very explanatory approach if there is a strict protocol, monitoring and measures to improve compliance, with specific advice on allowed co-interventions and complications.
* Flexibility (adherence): How different is the flexibility in how participants must adhere to the intervention and the flexibility likely in usual care? For example, score 5 for a very pragmatic choice involving no more than usual encouragement to adhere to the intervention; score 1 for a very explanatory approach that involves exclusion based on adherence, and measures to improve adherence if found wanting. In some trials eg surgical trials where patients are being operated on or Intensive Care Unit trials where patients are being given IV drug therapy, this domain is not applicable as there is no compliance issue after consent has been given, so this score should be left blank.
* Follow-up: How different is the intensity of measurement and follow-up of participants in the trial and the likely follow-up in usual care? For example, score 5 for a very pragmatic approach with no more than usual follow up; score 1 for a very explanatory approach with more frequent, longer visits, unscheduled visits triggered by primary outcome event or intervening event, and more extensive data collection.
* Primary outcome: To what extent is the trial's primary outcome relevant to participants? For example, score 5 for a very pragmatic choice where the outcome is of obvious importance to participants; score 1 for a very explanatory approach using a surrogate, physiological outcome, central adjudication or use assessment expertise that is not available in usual care, or the outcome is measured at an earlier time than in usual care.
* Primary analysis: To what extent are all data included in the analysis of the primary outcome? For example, score 5 for a very pragmatic approach using intention to treat with all available data; score 1 for a very explanatory analysis that excludes ineligible post-randomisation participants, includes only completers or those following the treatment protocol.
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User prompt

This is the full text to be assessed:
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%FULLTEXT%
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For each of the 9 domains of PRECIS-2, perform the following steps:
1. Extract 1-3 relevant quotes from the full text.
2. Explain your reasoning in 1 paragraph.
3. Give a score X from 1 (very explanatory) to 5 (very pragmatic) in square brackets like this: "Score: [X]". If the full text does not contain enough information to assess a specific domain, report "Score: [NA]".

Do not provide a final summary paragraph in the end.